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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 181 records · Page 10Linked to original sources
PubMed1998

Intracortical functional heterogeneity in area striate during penicillin-induced spikes in rabbits.

The generation and spread of epileptiform activity within the cortex depend on the functional and anatomical relationships between the focus and its surrounding area. These processes are not completely understood. Thus intracortical current-source-density analysis (CSD) was performed in six rabbits in order to investigate this functional relationship. Electric potential was measured perpendicular to the cortical surface by means of two 16-channel probes, and CSD was calculated within the focus and at various distances of up to 5 mm. The cortical areas surrounding the focus could be subdivided into three regions. The region up to 3 mm from the focus showed similar activity but beyond 4.5 mm no characteristic functional relationship was found with regard to the epileptiform events within the focus. Within the region 3.5-4.5 mm, however, mainly supragranular cells seem to contribute to the electric potential measured at the cortical surface and within the extracellular space. They were activated simultaneously with the initiation of focal spike generation. Taking into account the distribution of the electric potential and the results of CSD analysis, these cells seem mainly involved in the inhibition of the horizontal spread of spike activity.

Action Potentials↗
PubMed1998

Bacterial DNA as immune cell activator.

Pattern recognition receptors of the innate and adaptive immune systems apparently recognize unmethylated CpG motifs of bacterial DNA. Cells of the innate immune system are activated directly by CpG motifs, and the resulting response dictates a Th1 bias to the developing adaptive immune response. Interestingly, antigen receptor occupancy of cells of the adaptive immune system augments their responsiveness to CpG motifs, suggesting that co-stimulatory mechanisms are operative.

Animals↗
PubMed1998

Arthritis and sepsis caused by Staphylococcus aureus: can the tissue injury be reduced by modulating the host's immune system?

In recent years, a number of virulence factors that are either expressed, secreted or sequestered by staphylococci have been shown to affect the outcome of the infective process. Secretion of superantigens and exposure of the immune system to sequestered bacterial DNA aggravates the inflammatory response of the infected host to a point that can be life threatening. This exaggerated inflammatory response is mediated by cytokines originating from activated T cells and macrophages. Recent studies show that downregulation of lymphocyte and macrophage responses (e.g. by treatment with corticosteroids) significantly alleviates the outcome of staphylococcal infections when combined with appropriate antibiotics.

Animals↗
PubMed1998

New acetylenes isolated from the bark of Heisteria acuminata.

Five new linear acetylenic compounds, namely, pentadeca-6,8,10-triynoic acid (1), octadeca-8,10,12-triynoic acid (2), trans-pentadec-10-en-6,8-diynoic acid (3), cis-hexadec-11-en-7,9-diynoic acid (4), and cis-octadec-12-en-7,9-diynoic acid (5), were isolated from the bark of Heisteria acuminata by bioassay-guided fractionation, using cyclooxygenase (COX) and 5-lipoxygenase (5-LO) assays as models for antiinflammatory activity. The structures of compounds 1-5 were established by NMR, MS, IR, and Raman spectroscopy. These isolated compounds were found to be potent inhibitors of COX. Compounds 4 and 5 were the most potent inhibitors of 5-LO, whereas the other compounds only showed a weak inhibition at the same concentration.

Acetylene↗
PubMed1998

A therapeutic trial of radiation therapy with Vincristine, etoposide, and Procarbazine (VVP) in high grade intracranial gliomas--an Eastern Cooperative Oncology Group Study (E2392).

This study is a combined modality Phase II therapeutic trial to determine the efficacy of the novel combination of VP-16, Vincristine and Procarbazine in addition to postoperative radiation therapy in patients with high grade intracranial gliomas. Thirty three patients (median age 51 years) were entered (27 with glioblastoma multiforme, 6 with anaplastic astrocytoma). Toxicity was manageable with no lethal toxicities. Five of seven life threatening toxicities were hematologic. Median overall survival was 14.2 months. These data suggest this regimen is effective treatment for patients with high grade gliomas.

Administration, Oral↗
PubMed1998

Activation of macrophages and B lymphocytes by an oligodeoxynucleotide derived from an acutely pathogenic simian immunodeficiency virus.

Certain CpG-containing DNA sequences from bacteria, viruses, or invertebrates elicit responses in the vertebrate innate immune system. These responses also account for many nonspecific effects of oligodeoxynucleotides used for antisense approaches. Here we describe a sequence from an acutely pathogenic simian immunodeficiency virus (SIV) that induces release of cytokines from macrophages and B lymphocyte proliferation. Furthermore, several similar sequences in other immunodeficiency viruses were found that also activate macrophages. These results led to the question if CpG-containing DNA, which is thought to play an immunostimulatory role in bacterial infections, has a similar role in infections by immunodeficiency viruses.

Animals↗
PubMed1998

Enhancing the role of radiotherapy in non-small cell lung cancer.

Radiation therapy plays an important role in the treatment of patients with unresectable non-small cell lung cancer. Local control rates with past radiation therapy techniques have been poor, in the range of 10% to 15%. Recent advances in dose planning and delivery, as well as radiation biology, offer the promise of improved control and better protection of dose limiting normal tissues.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

Unilateral Peters' anomaly complicated by a corneal tattoo.

Anterior segment dysgenesis is characterized by a spectrum of congenital anomalies involving the cornea, the iris, and the anterior chamber angle; it may be further complicated by systemic anomalies and glaucoma. Peters' anomaly, a specific type of mesenchymal anterior segment dysgenesis, is characterized by a central corneal leukoma, iridocorneal adhesions, and abnormalities of the posterior corneal stroma, Descemet's membrane, corneal endothelium, lens, and anterior chamber. Eighty percent of the cases are bilateral. We present an unusual unilateral case of Peters' anomaly complicated by postsurgical ocular muscle deviation, an iatrogenic corneal tattoo, cataract, and papillary conjunctivitis associated with contact lens wear. This article illustrates the classification of variants of anterior segment dysgenesis and the technique of corneal tatooing, as well as the use of prosthetic contact lenses in the management of corneal opacities. We stress that successful management of Peters' anomaly requires proper diagnosis of the condition, age-appropriate treatment with surgical consultation, and careful follow-up in affected patients.

Adult↗
PubMed1998

Essential role of gamma interferon in survival of colon ascendens stent peritonitis, a novel murine model of abdominal sepsis.

Despite considerable progress, peritonitis and sepsis remain life-threatening conditions. To improve the understanding of the pathophysiology encountered in sepsis, a new standardized and highly reproducible murine model of abdominal sepsis termed colon ascendens stent peritonitis (CASP) was developed. In CASP, a stent is inserted into the ascending colon, which generates a septic focus. CASP employing a stent of 14-gauge diameter (14G stent) results in a mortality of 100% within 18 to 48 h after surgery. By inserting stents of small diameters, mortality can be exactly controlled. Thus, CASP surgery with insertion of a 22G or 18G stent (22G or 18G CASP surgery) results in 38 or 68% mortality, respectively. 14G CASP surgery leads to a rapid invasion of bacteria into the peritoneum and the blood. As a consequence, endotoxemia occurs, inflammatory cells are recruited, and a systemic inflammatory response syndrome develops. Interestingly, the most pronounced upregulation of inflammatory cytokines (gamma interferon [IFN-gamma], tumor necrosis factor alpha [TNF-alpha] and interleukin-12) is observed in spleen and lungs. CASP surgery followed by stent removal at specific time intervals revealed that all animals survived if intervention was performed after 3 h, whereas removal of the septic focus after 9 h did not prevent death, suggesting induction of autonomous mechanisms of a lethal inflammatory response syndrome. 18G CASP surgery in IFN-gamma receptor-deficient (IFNgammaR-/-) mice revealed an essential role of IFN-gamma in survival of sepsis, whereas TNF receptor p55-deficient (TNFRp55-/-) mice did not show altered survival rates. In summary, this study describes a novel animal model that closely mimics human sepsis and appears to be highly suitable for the study of the pathophysiology of abdominal sepsis. Importantly, this model demonstrates a protective role of IFN-gamma in survival of bacterial sepsis.

Abdomen↗
PubMed1998

Effect of prolonged heavy exercise on pulmonary gas exchange in horses.

During short-term maximal exercise, horses have impaired pulmonary gas exchange, manifested by diffusion limitation and arterial hypoxemia, without marked ventilation-perfusion (VA/Q) inequality. Whether gas exchange deteriorates progressively during prolonged submaximal exercise has not been investigated. Six thoroughbred horses performed treadmill exercise at approximately 60% of maximal oxygen uptake until exhaustion (28-39 min). Multiple inert gas, blood-gas, hemodynamic, metabolic rate, and ventilatory data were obtained at rest and 5-min intervals during exercise. Oxygen uptake, cardiac output, and alveolar-arterial PO2 gradient were unchanged after the first 5 min of exercise. Alveolar ventilation increased progressively during exercise, from increased tidal volume and respiratory frequency, resulting in an increase in arterial PO2 and decrease in arterial PCO2. At rest there was minimal VA/Q inequality, log SD of the perfusion distribution (log SDQ) = 0.20. This doubled by 5 min of exercise (log SDQ = 0.40) but did not increase further. There was no evidence of alveolar-end-capillary diffusion limitation during exercise. However, there was evidence for gas-phase diffusion limitation at all time points, and enflurane was preferentially overretained. Horses maintain excellent pulmonary gas exchange during exhaustive, submaximal exercise. Although VA/Q inequality is greater than at rest, it is less than observed in most mammals and the effect on gas exchange is minimal.

Animals↗
PubMed1998

Angiogenic growth factor mRNA responses to passive and contraction-induced hyperperfusion in skeletal muscle.

It has been proposed that, in skeletal muscle, the angiogenic response to exercise may be signaled by the increase in muscle blood flow, via biomechanical changes in the microcirculation (increased shear stress and/or wall tension). To examine this hypothesis, we compared the change in abundance of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta1 (TGF-beta1) mRNA in skeletal muscles of the canine leg after 1 h of pump-controlled high blood flow alone (passive hyperperfusion; protocol A) and electrical stimulation of the femoral and sciatic nerves producing muscle contraction (protocol B). The increase in leg blood flow (5.4- and 5. 9-fold change from resting values, respectively) was similar in both groups. Passive hyperperfusion alone did not increase message abundance for VEGF (ratio of mRNA to 18S signals after vs. before hyperperfusion, 0.94 +/- 0.08) or bFGF (1.08 +/- 0.05) but slightly increased that of TGF-beta1 (1.14 +/- 0.07; P < 0.03). In contrast, as previously found in the rat, electrical stimulation provoked more than a threefold increase in VEGF mRNA abundance (3.40 +/- 1.45; P < 0.02). However, electrical stimulation produced no significant changes in either bFGF (1.16 +/- 0.13) or TGF-beta1 (1.31 +/- 0.27). These results suggest that the increased muscle blood flow of exercise does not account for the increased abundance of these angiogenic growth factor mRNA levels in response to acute exercise. We speculate that other factors, such as local hypoxia, metabolite concentration changes, or mechanical effects of contraction per se, may be responsible for the effects of exercise.

Animals↗
PubMed1998

Effect of prolonged, heavy exercise on pulmonary gas exchange in athletes.

During maximal exercise, ventilation-perfusion inequality increases, especially in athletes. The mechanism remains speculative. We hypothesized that, if interstitial pulmonary edema is involved, prolonged exercise would result in increasing ventilation-perfusion inequality over time by exposing the pulmonary vascular bed to high pressures for a long duration. The response to short-term exercise was first characterized in six male athletes [maximal O2 uptake (V(O2)max) = 63 ml x kg-1 x min-1] by using 5 min of cycling exercise at 30, 65, and 90% V(O2) max. Multiple inert-gas, blood-gas, hemodynamic, metabolic rate, and ventilatory data were obtained. Resting log SD of the perfusion distribution (log SDQ) was normal [0.50 +/- 0.03 (SE)] and increased with exercise (log SDQ = 0.65 +/- 0.04, P < 0.005), alveolar-arterial O2 difference increased (to 24 +/- 3 Torr), and end-capillary pulmonary diffusion limitation occurred at 90% V(O2)max. The subjects recovered for 30 min, then, after resting measurements were taken, exercised for 60 min at approximately 65% V(O2)max. O2 uptake, ventilation, cardiac output, and alveolar-arterial O2 difference were unchanged after the first 5 min of this test, but log SDQ increased from 0.59 +/- 0.03 at 5 min to 0. 66 +/- 0.05 at 60 min (P < 0.05), without pulmonary diffusion limitation. Log SDQ was negatively related to total lung capacity normalized for body surface area (r = -0.97, P < 0.005 at 60 min). These data are compatible with interstitial edema as a mechanism and suggest that lung size is an important determinant of the efficiency of gas exchange during exercise.

Adult↗
PubMed1998

GABAergic inhibition influences auditory motion-direction sensitivity in barn owls.

Many neurons in the barn owl's inferior colliculus (IC) exhibit auditory motion-direction sensitivity (MDS), i.e., they respond more to motion of a sound source in one direction than to motion in the opposite direction. We investigated the cellular mechanisms underlying the phenomenon of auditory MDS by microiontophoretically applying gamma-aminobutyric acid (GABA) or the GABA-antagonist bicuculline methiodide (BMI) while recording from neurons in the owl's midbrain. In most cases GABA reduced the overall firing rate, whereas BMI increased it. In addition, 29% of the motion-direction-sensitive cells completely lost their selectivity for the direction of auditory movement during administration of BMI. It had been proposed that auditory MDS in the owl is due to inhibition. The present results show that GABAergic inhibition plays a role in the strengthening of MDS. We discuss the data within the framework of the acoustic motion detector and with respect to microiontophoretic studies on visual motion detection and on inhibitory mechanisms in the inferior colliculus.

Acoustic Stimulation↗
PubMed1998

Session summary

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Journal Article↗
PubMed1998

Phase II trial of hyperfractionated accelerated radiation therapy for nonresectable non-small-cell lung cancer: results of Eastern Cooperative Oncology Group 4593.

PURPOSE: To assess the feasibility, toxicity, and efficacy of hyperfractionated accelerated radiation therapy (HART) for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty patients from six institutions with stage IIIA or IIIB NSCLC were enrolled between November 1993 and August 1995. Radiation therapy (total dose, 57.6 Gy in 36 fractions) was delivered over 15 days with the use of three daily fractions with a 4-hour interval between fractions and an 8-hour interval between on-cord fields. Patients were not treated on weekends. RESULTS: Twenty-eight patients (93%) completed radiation therapy. Treatment-related toxicities of grade 3 or greater included esophagitis in six patients and grade 3 skin reaction in three patients. The overall objective response rate was 54%, and the response rate within the radiation field was 64%. With a minimum follow-up of 19 months in surviving patients, the median survival and 1-year survival rate are 13 months and 57%, respectively. The median relapse-free survival and 1-year relapse-free survival rate are 7 months and 23%, respectively. No transverse myelitis or late toxicities of grade 4 or greater have been observed. CONCLUSION: HART, delivered to a total dose of 57.6 Gy over 15 total days, is practical and well tolerated. Survival appears similar to that seen with modern combined modality regimens. A phase III trial is under way.

Aged↗
PubMed1998

Radiation therapy in the management of limited small cell lung cancer: when, where, and how much?

Progress in the treatment of patients with small cell lung cancer (SCLC) has come in two phases. In the first phase, SCLC was recognized, even when seemingly localized to the lung and intrathoracic lymph nodes, to be widely metastatic and to require effective systemic therapy from the outset. The development of active chemotherapeutic agents and combinations in the 1970s improved median survival from the 6 months seen with radiotherapy alone to about 1 year. In the second phase has come the recognition that local control of a disease, even one with systemic spread, is necessary for its cure. This has resulted both in a better appreciation of the role of radiation therapy in SCLC treatment and in efforts to optimize combined-modality regimens using radiotherapy and chemotherapy. With current treatment regimens involving concurrent or closely interdigitated administration of cisplatin and etoposide chemotherapy and radiation doses of 45 Gy given over 3 to 5 weeks, median survivals of 20 to 24 months have been reported by many single institutions and confirmed in large cooperative group trials. Issues remaining to be resolved include optimization of radiation dose, volume, and timing; the role of prophylactic cranial irradiation; and how to reduce acute and late toxic reactions of treatment. As we develop more specific therapies based on specific molecular and biological characteristics of SCLC, including its autocrine growth regulation, we will be challenged to integrate these successfully with current radiation and chemotherapeutic approaches.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study.

PURPOSE: To describe the baseline findings in patients enrolled in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. METHODS: This is a longitudinal observational study of 1209 patients with keratoconus enrolled at 16 clinical centers. Its main outcome measures are corneal scarring, visual acuity, keratometry, and quality of life. RESULTS: The CLEK Study patients had a mean age of 39.29+/-10.90 years with moderate to severe disease, assessed by a keratometric-based criterion (95.4% of patients had steep keratometric readings of at least 45 D) and relatively good visual acuity (77.9% had best corrected visual acuity of at least 20/40 in both eyes). Sixty-five percent of the patients wore rigid gas-permeable contact lens, and most of those (73%) reported that their lenses were comfortable. Only 13.5% of patients reported a family history of keratoconus. None reported serious systemic diseases that had been previously reported to be associated with keratoconus. Many (53%) reported a history of atopy. Fifty-three percent had corneal scarring in one or both eyes. CONCLUSIONS: Baseline findings suggest that keratoconus is not associated with increased risk of connective tissue disease and that most patients in the CLEK Study sample represent mild to moderate keratoconus. Additional follow-up of at least 3 years will provide new information about the progression of keratoconus, identify factors associated with progression, and assess its impact on quality of life.

Adult↗