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Biomedical subjects

A May

Publications and source records attributed to A May.

At least 127 records · Page 7Linked to original sources
PubMed1999

Endoscopic therapeutic esophageal interventions.

Cyanoacrylat and fibrin glue seem to be no better alternatives to ligation in the treatment of bleeding esophageal varices. Studies with photodynamic therapy (PDT) of high-grade dysplasia (HGD) and early esophageal cancer show encouraging results. The use of 5-aminolaevulinic acid (ALA) as a photosensitizer minimizes the rate of severe side effects, but only in HGD and tumors with a depth of 2 mm or less can a complete remission be achieved. The use of Lugol's iodine solution is sensible for the detection of HGD and early squamous cell cancers. Thermal ablation with Neodym:YAG laser and self-expanding metal stents are the most important modalities for palliative treatment of esophageal cancer.

Journal Article↗
PubMed1999

The trigeminovascular system in humans: pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation.

Primary headache syndromes, such as cluster headache and migraine, are widely described as vascular headaches, although considerable clinical evidence suggests that both are primarily driven from the brain. The shared anatomical and physiologic substrate for both of these clinical problems is the neural innervation of the cranial circulation. Functional imaging with positron emission tomography has shed light on the genesis of both syndromes, documenting activation in the midbrain and pons in migraine and in the hypothalamic gray in cluster headache. These areas are involved in the pain process in a permissive or triggering manner rather than as a response to first-division nociceptive pain impulses. In a positron emission tomography study in cluster headache, however, activation in the region of the major basal arteries was observed. This is likely to result from vasodilation of these vessels during the acute pain attack as opposed to the rest state in cluster headache, and represents the first convincing activation of neural vasodilator mechanisms in humans. The observation of vasodilation was also made in an experimental trigeminal pain study, which concluded that the observed dilation of these vessels in trigeminal pain is not inherent to a specific headache syndrome, but rather is a feature of the trigeminal neural innervation of the cranial circulation. Clinical and animal data suggest that the observed vasodilation is, in part, an effect of a trigeminoparasympathetic reflex. The data presented here review these developments in the physiology of the trigeminovascular system, which demand renewed consideration of the neural influences at work in many primary headaches and, thus, further consideration of the physiology of the neural innervation of the cranial circulation. We take the view that the known physiologic and pathophysiologic mechanisms of the systems involved dictate that these disorders should be collectively regarded as neurovascular headaches to emphasize the interaction between nerves and vessels, which is the underlying characteristic of these syndromes. Moreover, the syndromes can be understood only by a detailed study of the cerebrovascular physiologic mechanisms that underpin their expression.

Animals↗
PubMed1999

Eosinophilic cationic protein as a marker of nasal inflammation in patients with cystic fibrosis.

OBJECTIVES: Evaluation was made of eosinophilic cationic protein (ECP) in nasal secretion for measuring the degree of nasal inflammation and monitoring response to therapy in cystic fibrosis (CF) patients with chronic rhinosinusitis. Symptoms and findings in regard to ECP levels before and after treatment were described. STUDY DESIGN: Study was prospective, with 21 CF patients aged 4 to 19 years; 20 healthy volunteers served as controls. Collection of nasal secretion by a sponge was performed, and blood samples were obtained for serum. Cystic fibrosis (CF) patients were classified according to nasal symptoms and findings. METHODS: ECP was measured by fluoroimmunoassay. Age, sex, nasal symptoms, and endoscopic and histological findings were obtained, and examinations were conducted before and after treatment; recurrences were recorded. RESULTS: In CF patients with chronic nasal inflammation, increased nasal levels of ECP were detected when compared with asymptomatic CF patients or healthy nonatopic subjects. ECP concentrations were strongly related to the extent of nasal disease; patients with nasal polyps had higher levels than those without. Checked at 1 and 4 months after treatment, ECP levels declined with regression of symptoms, and in patients with exacerbation of nasal disease, ECP levels rose. CONCLUSIONS: According to our study, there is a relationship between levels of ECP in nasal secretions and the degrees of nasal inflammation. In addition, the measurement of ECP could be useful in monitoring nasal disease in CF patients.

Adolescent↗
PubMed1999

Lysine-acetylsalicylic acid in acute migraine attacks.

Vasoconstrictive agents have been widely used in the treatment of migraine. These types of drugs have various side effects and are not suitable for many patients. Due to nausea or vomiting, nonoral treatment is often required, but only a few nonvasoconstrictive drugs exist in a parenteral form and are suitable for the treatment of acute migraine in the emergency setting. In a randomized, double-blind, crossover trial we evaluated the efficacy of 1,000 mg lysine-acetylsalicylic acid i.v. (LAS) compared to 0.5 mg ergotamine s.c. in 56 patients (112 attacks) with acute migraine. To gain further insight into the possible role of vasoconstriction, blood flow velocities (BFV) were measured in intra- and extracranial arteries using duplex sonography and transcranial Doppler sonography. Both agents were equally potent in relieving headache. Intravenous LAS resulted in a significantly faster relief and had fewer side effects. LAS had no effect on BFV. Ergotamine increased BFV in the middle cerebral artery only. No correlation was found between changes in BFV and the relief of headache. This is the first trial to compare the intravenous formulation of LAS in the treatment of migraine with another antimigraine medication and suggests that it is an effective and safe drug for the parenteral treatment of acute migraine attacks.

Acute Disease↗
PubMed1999

[Optimized extracorporeal shockwave lithotripsy of gallbladder calculi: a prospective randomized therapy comparison].

UNLABELLED: Is "pulverization" or "fragmentation" the best endpoint of extracorporeal shock wave application in ESWL of gallbladder stones? Has gallbladder motility a potential for the prevention of stone recurrence? METHODS: Prospective, monocentric study with randomization between the conventional treatment strategy (endpoint of shock wave application: fragments < or = 4 mm, concomitant oral chemolitholysis) and an intensified treatment strategy (endpoint of shock wave application: Pulverization, no chemolitholysis). Prevention of stone recurrence: At least once per month for one hour after a meal standardized position (back position, lowered chest). RESULTS: 34 patients, age 46 +/- 14 years (27 women, seven men) were included (F-ESWL: n = 18; P-ESWL: n = 16). Gallbladder motility, number, size and CT-measured calcifications of stones were comparable for both groups. P-ESWL patients received more shock wave pulses than F-ESWL patients and more treatment sessions. P-ESWL resulted in a better fragmentation and pulverization of stones was reached significantly more often (p < 0.05). The time period for stone clearance was significantly depending on the fragmentation result (pulverization: 0.7 months vs. fragments < or = 4 mm: 6.6 months vs. fragments > or = 4 mm: 8.0 months; p < 0.01). The stone free rate after twelve months was 87.5% for P-ESWL and 72.2% for F-ESWL (n.s.) and correlated significantly with the fragmentation result (p < 0.01). Pain sensations during stone clearance were significantly reduced by P-ESWL. Stonefree patients were followed up for 30 +/- 13 months, the total recurrence rate was 7.1%. CONCLUSIONS: Aiming for pulverization of gallbladder stones by means of intensified extracorporeal shock wave application is at least equal or in tendency superior compared to disintegration to fragements < or = 4 mm. Gallbladder motility might be useful to prevent gallstone recurrence after successful ESWL.

Adult↗
PubMed1998

Efficient PCNA complex formation is dependent upon both transcription coupled repair and genome overall repair.

The protein proliferating cell nuclear antigen (PCNA) is an auxiliary factor for DNA polymerase delta and is involved in the resynthesis step of nucleotide excision repair (NER). After UV irradiation of quiescent cells, PCNA forms an insoluble complex with nuclear substructures. We have investigated associations between NER and its subcomponent pathway, transcription coupled repair (TCR) on PCNA complex formation using genetically related hamster cell lines with different repair characteristics. In DNA repair proficient cells, the PCNA complex was readily detectable within 30 min after UV irradiation by both immunofluorescence and western blot analyses. This complex formation after UV occurs efficiently in quiescent cells. In UV5 (human XP-D homolog) and UV 24 (human XP-B homolog) cells, which are totally deficient in NER, the PCNA complex was not detectable at 30 min after UV. The PCNA complex formation is restored to normal levels in UV5 cells after transfection with the human XPD gene, encoding a subunit of the basal transcription factor, TFIIH. In UV61 (Human CS-B homolog) cells, that are defective only in transcription coupled repair (TCR) of cyclobutane pyrimidine dimers (CPDs), the rate of PCNA complex formation was 2-fold slower than in repair proficient cells. This defect was complemented by transfection of the CSB gene into the UV61 cells. We thus conclude that efficient PCNA complex formation after UV is dependent upon both the NER and TCR pathways in hamster cells. The association of several other DNA repair proteins including XPA, RPA, TFIIH and p53 with the insoluble PCNA complex in UV treated cells suggests a central role for PCNA in different steps of NER.

Animals↗
PubMed1998

Fine structural analysis of DNA repair in mammalian cells.

Nucleotide excision repair (NER) of ultraviolet (UV) light induced photo lesions is heterogeneous in the genomic DNA. We have investigated the mechanistic basis for this repair heterogeneity by analyzing NER activity in higher order chromatin of repair proficient hamster cells. Immunological labeling of repair and transcription sites indicates that NER initiates at the nuclear matrix in close association with transcription. The repair gradually extends into the loop DNA regions in a time dependent fashion. Repair analysis indicates that the DNA damaged by UV irradiation is recruited to the nuclear matrix soon after UV exposure. Consistent with this finding, immunofluorescence and western blotting analyses indicate the enrichment of many NER proteins (XPA, RPA, PCNA, the P62 and p89 sub-units of the basal transcription factor, TFIIH) in the nuclear matrix of UV treated cells. These results strengthen the notion that the nuclear matrix is an important site for the assembly of an efficient repair complex.

Animals↗
PubMed1998

Hypothalamic activation in cluster headache attacks.

BACKGROUND: Cluster headache, one of the most severe pain syndromes in human beings, is usually described as a vascular headache. However, the striking circadian rhythmicity of this strictly half-sided pain syndrome cannot be readily explained by the vascular hypothesis. We aimed to assess changes in regional cerebral blood flow (rCBF) in patients with cluster headache. METHODS: We used positron emission tomography (PET) to assess the changes in rCBF, as an index of synaptic activity, during nitroglycerin-induced cluster headache attacks in nine patients who had chronic cluster headache. Eight patients who had cluster headache but were not in the bout acted as a control group. FINDINGS: In the acute pain state, activation was seen in the ipsilateral inferior hypothalamic grey matter, the contralateral ventroposterior thalamus, the anterior cingulate cortex, and bilaterally in the insulae. Activation in the hypothalamus was seen solely in the pain state and was not seen in patients who have cluster headache but were out of the bout. INTERPRETATION: Our findings establish central nervous system dysfunction in the region of the hypothalamus as the primum movens in the pathophysiology of cluster headache. We suggest that a radical reappraisal of this type of headache is needed and that it should in general terms, be regarded as a neurovascular headache, to give equal weight to the pathological and physiological mechanisms that are at work.

Adult↗
PubMed1998

Effect of aging on EGF-stimulated replication of specific genes in rat hepatocytes.

EGF-stimulated replication of specific genes was examined in primary hepatocyte cultures from mature (6 months) and senescent (24 months) rats. Basal and EGF-stimulated [3H]thymidine incorporation and DNA polymerase alpha activities, as well as total cellular DNA, were also assessed. The genes examined were dihydrofolate reductase (DHFR) and c-myc, as well as total mitochondrial DNA (mt DNA). Although [3H]thymidine incorporation, DNA polymerase alpha activity, total cellular DNA, DHFR, and c-myc gene specific DNA replication stimulated by EGF are reduced with age, mt DNA replication is not affected by either EGF or age. Chromosomal DNA replication is mediated mainly by DNA polymerase alpha while mt DNA replication is mediated by its own DNA polymerase gamma. Thus, the age-related decline in stimulated DNA replication appears to be associated mainly with the DNA polymerase alpha activation pathway.

Aging↗
PubMed1998

Photodynamic ablation of high-grade dysplasia and early cancer in Barrett's esophagus by means of 5-aminolevulinic acid.

BACKGROUND & AIMS: The first therapeutic experiences with the conventional photosensitizer dihematoporphyrinester in the treatment of Barrett's esophagus show the curative potential of photodynamic therapy (PDT). The aim of this study was to test 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX, a photosensitizer with a high mucosa specificity without phototoxic side effects on the skin, as a new form of PDT. METHODS: Thirty-two patients (mean age, 68.5 years) with histologically proven high-grade dysplasia (n = 10) and mucosal cancer (n = 22) in Barrett's esophagus were treated. Four to 6 hours after oral ingestion of 5-ALA (dose, 60 mg/kg body wt), irradiation was conducted with a dye laser system (635 nm) with a light dose of 150 J/cm2. The patients received 20-80 mg omeprazole daily after PDT. RESULTS: High-grade dysplasia was eradicated in all patients (10 of 10), and mucosal cancer was eliminated in 17 of 22 patients (77%) at a mean follow-up of 9.9 months (range, 1-30 months). All tumors < or = 2 mm in thickness were completely ablated (17 of 17). The method-related mortality and morbidity was 0%. CONCLUSIONS: Severe dysplasia and thin (< or = 2 mm) mucosal cancer of Barrett's esophagus can be completely ablated. PDT might offer a minimally invasive treatment modality as an alternative to esophagectomy.

Adult↗
PubMed1998

Experimental cranial pain elicited by capsaicin: a PET study.

Using a positron emission tomography (PET) study it was shown recently that in migraine without aura certain areas in the brain stem were activated during the headache state, but not in the headache free interval. It was suggested that this brain stem activation is inherent to the migraine attack itself and represents the so called 'migraine generator'. To test this hypothesis we performed an experimental pain study in seven healthy volunteers, using the same positioning in the PET scanner as in the migraine patients. A small amount of capsaicin was administered subcutaneously in the right forehead to evoke a burning painful sensation in the first division of the trigeminal nerve. Increases of regional cerebral blood flow (rCBF) were found bilaterally in the insula, in the anterior cingulate cortex, the cavernous sinus and the cerebellum. Using the same stereotactic space limits as in the above mentioned migraine study no brain stem activation was found in the acute pain state compared to the pain free state. The increase of activation in the region of the cavernous sinus however, suggests that this structure is more likely to be involved in trigeminal transmitted pain as such, rather than in a specific type of headache as was suggested for cluster headache.

Acute Disease↗
PubMed1998

Ras pathway activates epithelial Na+ channel and decreases its surface expression in Xenopus oocytes.

The small G protein K-Ras2A is rapidly induced by aldosterone in A6 epithelia. In these Xenopus sodium reabsorbing cells, aldosterone rapidly activates preexisting epithelial Na+ channels (XENaC) via a transcriptionally mediated mechanism. In the Xenopus oocytes expression system, we tested whether the K-Ras2A pathway impacts on XENaC activity by expressing XENaC alone or together with XK-Ras2A rendered constitutively active (XK-Ras2AG12V). As a second control, XENaC-expressing oocytes were treated with progesterone, a sex steroid that induces maturation of the oocytes similarly to activated Ras. Progesterone or XK-Ras2AG12V led to oocyte maturation characterized by a decrease in surface area and endogenous Na+ pump function. In both conditions, the surface expression of exogenous XENaC's was also decreased; however, in comparison with progesterone-treated oocytes, XK-ras2AG12V-coinjected oocytes expressed a fivefold higher XENaC-mediated macroscopic Na+ current that was as high as that of control oocytes. Thus, the Na+ current per surface-expressed XENaC was increased by XK-Ras2AG12V. The chemical driving force for Na+ influx was not changed, suggesting that XK-Ras2AG12V increased the mean activity of XENaCs at the oocyte surface. These observations raise the possibility that XK-Ras2A, which is the first regulatory protein known to be transcriptionally induced by aldosterone, could play a role in the control of XENaC function in aldosterone target cells.

Aldosterone↗
PubMed1998

Retinal plasma extravasation in animals but not in humans: implications for the pathophysiology of migraine.

High-intensity electrical stimulation of the trigeminal ganglion is accompanied by mast cell degranulation, vasodilatation, increased endothelial permeability and leakage of albumin from postcapillary venules within the dura mater. Overall, the histological appearance suggests an evolving sterile inflammatory response. This neurogenic inflammation within the meninges has been suggested as a model to explain the pain in migraine and cluster headache, and has been used to characterize the pharmacology of anti-migraine compounds. Using the rat model of neurogenic inflammation, the albumin extravasation ratio (stimulated : unstimulated side) in vehicle-treated animals in the dura and retina was 1.60 +/- 0.11 and 1.76 +/- 0.18, respectively (n = 10; values are mean +/- SEM). Pretreatment with sumatriptan (n = 9) produced a highly significant reduction in the ratio of extravasation within the dura to 1.10 +/- 0.06 (P = 0.002) and in the retina to 0.96 +/- 0.06 (P = 0.001), as did the neurokinin-1 receptor antagonist RP 67580 (n = 12) in the dura (1.04 +/- 0.11, P = 0.002) and retina (1.08 +/- 0.06, P = 0.001). These data demonstrate increased endothelial permeability and leakage of albumin not only in the dura but also in the retina. In a second stage we investigated possible extravasation in the human retina in acute migraine (n = 8) and cluster headache (n = 5) using fluorescein or indocyanine angiography. No increased endothelial permeability or leakage of dye could be found in the human retinal or choroidal vessels during headache attacks or in the headache-free interval in persons suffering from both migraine and cluster headache. These data raise the possibility that neurogenic inflammation is not a major factor in headache attacks in migraine or cluster headache.

Adult↗
PubMed1998

Cluster headache: imaging and other developments.

Cluster headache, one of the most severe pain syndromes in humans, is usually described as a vascular headache. However, the striking circadian rhythmicity of this strictly unilateral pain syndrome cannot readily be explained by the vascular hypothesis. Recent studies using positron emission tomography suggest that a central nervous system dysfunction in the region of the hypothalamus is the primum movens in the pathophysiology of cluster headache. From a physiological viewpoint, therefore, cluster headache should be described as a neurovascular headache, thus placing equal emphasis on its fundamental pathophysiology and clinical expression.

Circadian Rhythm↗
PubMed1998

Palliative treatment of malignant esophagorespiratory fistulas with Gianturco-Z stents. A prospective clinical trial and review of the literature on covered metal stents.

OBJECTIVE: Esophagorespiratory fistulas, especially in the upper third of the esophagus, are a complication of malignant esophageal tumors, which are difficult to manage. The efficacy of polyurethane-covered, self-expanding metal stents for palliation of malignant esophagorespiratory fistulas was investigated prospectively. METHODS: Eleven patients with malignant esophagorespiratory fistulas resp. perforations were treated with Gianturco-Z stents. In five patients the lesion was located in the proximal part of the esophagus. Because of the fistula all patients suffered from dysphagia even for liquids. RESULTS: No technical problems during the implantation procedure of the stents occurred. In the control radiography with water-soluble contrast media, the fistulas were completely sealed in 10 of 11 patients. Therefore the dysphagia score improved from 3.0 to 0.6. Nearly all Gianturco-Z stents (10/11) showed a sufficient expansion within 24 h after placement. Severe early or late complications were not encountered, with the exception of tumor overgrowth in one patient about 9 months after stent placement. In five patients, short term (3-6 days) retrosternal pain was observed, and one patient complained of slight foreign body sensation. By August 1997 all 11 patients had died of advanced disease, with a median survival time of 121 days (range, 22-300 days). CONCLUSIONS: Gianturco-Z stents are highly effective for palliative treatment of esophagorespiratory fistula resp. perforations and have a low complication rate. Due to the fact that this stent shows no retraction during the release, a precise positioning is possible, especially in the case of tumors and fistulas in the upper third of the esophagus. It seems that use of the Gianturco-Z stent can be considered a good therapeutic method for palliative endoscopic treatment of this high risk patient group.

Aged↗