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Biomedical subjects

J Pagel

Publications and source records attributed to J Pagel.

At least 19 recordsLinked to original sources

[The inhalation versus systemic prevention of pneumonitis during thoracic irradiation].

BACKGROUND: Pneumonitis is a typical subacute reaction of healthy bronchial tissue to thoracic irradiation. The purpose of the present trial was to show whether prophylactic application of steroids in the course of and following radiotherapy would reduce the incidence of pneumonitis. PATIENTS AND METHODS: Fifty-seven patients receiving thoracic irradiation for bronchial carcinoma were assigned to 2 therapeutic groups; half of the patients were given 10 mg of oral prednisolone per day, while the other half received daily inhalative beclomethasone. All patients were evaluated for radiographic signs of pneumonitis. Thirty-two patients received additional investigations for pulmonary diffusion capacity of carbon monoxide. RESULTS: The overall incidence of pneumonitis was 17.6% (10/57 patients). Neither total radiation dose nor mode of fractionation did significantly contribute to the incidence of pneumonitis. Those patients showing a pulmonary diffusion capacity for carbon monoxide of less than 60% prior to radiotherapy had a significantly higher risk of developing pneumonitis (4/7) than patients with a higher diffusion capacity (3/25, p = 0.026). In follow-up period we did not see significant changes in diffusion capacity neither with patients who developed pneumonitis nor with those patients showing no evidence of pulmonary injury. Comparing the chest X-ray there were less radiographic changes consistent with pneumonitis in the inhalative beclomethasone (2/28) than in the oral prednisolone group (8/29, p = 0.045). DISCUSSION: In order to reduce the incidence of pneumonitis in patients receiving thoracic irradiation we support a continuous application of steroids in the course of and following radiotherapy. The inhalative use of beclomethasone has proved to be superior to oral prednisolone due to better local efficacy and decreased unwanted side effects.

Administration, Inhalation↗

Functional analysis of DNA bending and unwinding by the high mobility group domain of LEF-1.

LEF-1 (lymphoid enhancer-binding factor 1) is a cell type-specific member of the family of high mobility group (HMG) domain proteins that recognizes a specific nucleotide sequence in the T cell receptor (TCR) alpha enhancer. In this study, we extend the analysis of the DNA-binding properties of LEF-1 and examine their contributions to the regulation of gene expression. We find that LEF-1, like nonspecific HMG-domain proteins, can interact with irregular DNA structures such as four-way junctions, albeit with lower efficiency than with specific duplex DNA. We also show by a phasing analysis that the LEF-induced DNA bend is directed toward the major groove. In addition, we find that the interaction of LEF-1 with a specific binding site in circular DNA changes the linking number of DNA and unwinds the double helix. Finally, we identified two nucleotides in the LEF-1-binding site that are important for protein-induced DNA bending. Mutations of these nucleotides decrease both the extent of DNA bending and the transactivation of the TCR alpha enhancer by LEF-1, suggesting a contribution of protein-induced DNA bending to the function of TCR alpha enhancer.

DNA, Superhelical↗

Early intervention and aggressive management of infected median sternotomy incision: a review of 2242 open-heart procedures.

Infected median sternotomy following open-heart surgery is a devastating complication with an incidence of 0.4 to 5 per cent and mortality as high as 80 per cent. Management varies from irrigation, debridement, closure with muscle, and skin flaps. We present our experience of early intervention and aggressive single-stage operative management. A retrospective chart review of all open-heart surgery patients was conducted from September 1984 through September 1994. Of the 2242 patients, 52 had infected median sternotomy incisions (2.3% incidence). The mean length of stay for reconstructive procedures was 18 days. The median interval to detection was 15 days, whereas the median interval to intervention was 4 days. There were five (6.8%) failed procedures and nine (12.3%) staged procedures. There were six deaths (11.5% incidence), one prior to receiving operative intervention. There was one false aneurysm. Single-stage reconstruction is safe, with results better than multistage procedures. It may be safely performed with a high success rate (93%). Early recognition and intervention significantly decreases length of stay.

Adult↗

Distinct DNA-binding properties of the high mobility group domain of murine and human SRY sex-determining factors.

The mammalian sex-determining gene SRY (sex-determining region on Y chromosome) encodes a member of the high mobility group (HMG) family of regulatory proteins. The HMG domain of the SRY protein represents a DNA binding motif that displays rather unusually weak evolutionary conservation of amino acids between human and mouse sequences. Together with the previous finding that the human (h) SRY gene is unable to induce a male phenotype in genetically female transgenic mice, these observations raise questions concerning the DNA binding properties of SRY proteins. Here, we present data that indicate that the DNA binding and bending properties of the HMG domains of murine (m) SRY and hSRY differ from each other. In comparison, mSRY shows more-extensive major-groove contacts with DNA and a higher specificity of sequence recognition than hSRY. Moreover, the extent of protein-induced DNA bending differs from the HMG domains of hSRY and mSRY. These differences in DNA binding by hSRY and mSRY may, in part, account for the functional differences observed with these gene products.

Animals↗

HMG domain proteins: architectural elements in the assembly of nucleoprotein structures.

The high-mobility group (HMG) domain is a DNA-binding motif that is shared abundant non-histone components of chromatin and by specific regulators of transcription and cell differentiation. The HMG family of proteins comprises members with multiple HMG domains that bind DNA with low sequence specificity, and members with single HMG domains that recognize specific nucleotide sequences. Common properties of HMG domain proteins include interaction with the minor groove of the DNA helix, binding to irregular DNA structures, and the capacity to modulate DNA structure by bending. DNA bending induced by the HMG domain can facilitate the formation of higher-order nucleoprotein complexes, suggesting that HMG domain proteins may have an architectural role in assembling such complexes.

Amino Acid Sequence↗

Bromocriptine in the treatment of carcinoma of the cervix: a phase II trial.

Twenty patients with advanced carcinoma of the uterine cervix were treated for at least 3 months with 5 mg bromocriptine daily. No remissions were found (95% confidence limits, 0-17%), neither among normo- nor among hyperprolactinemic patients. Twelve had stable disease for 2-9 months with a median of 3 months. The results of this study does not support the hypothesis that bromocriptine possesses any antitumor effect in cancer of the uterine cervix.

Adult↗

Transport patterns and complications in an isolated Alaska practice.

This study reviews the patterns of transport and complications that occurred in 169 cases of transporting patients over a four-year period for a small, isolated Alaskan community in which the physicians as a matter of policy attempted to avoid heroic emergency surgery. Case descriptions are included describing transport-related complications and mortality and morbidity of patients transferred. A low incidence of mortality and relatively little long-term morbidity was experienced, supporting the feasibility of transferring severely ill patients rather than attempting heroic surgery under marginal circumstances. Although the lack of comparable studies limits the usefulness of these findings in assessing the overall quality of care, appropriate utilization of transport as an extension of the physician's capabilities resulted in a low incidence of complications during the study period.

Adult↗

Acute hemorrhagic gastritis--diagnosis and treatment.

Approximately 10-20% of patients admitted with acute gastrointestinal bleeding suffer from hemorrhagic erosive gastritis. A material of 36 patients is presented and the literature reviewed. The moderate bleeders stop bleeding within hours to a few days and the majority may safely be managed conservatively, i.e. with blood transfusions. The severe bleeders continue to bleed for a long time and surgery is often required. Different operative procedures have been suggested. The mortality in this group of patients is high--nearly 30%, and the frequency of postoperative rebleeding is also high. It is concluded that there is no absolute operative procedure of choice but vagotomy combined with subtotal gastrectomy offer the best protection against rebleeding. Treatment with selective application of vasoconstrictors is mentioned.

Adult↗

The Mallory-Weiss syndrome.

During a 41/2-year period, 1970-74, 174 patients with upper gastro-intestinal bleeding were admitted to the Department of Surgical Gastroenterology, Rigshospitale, Copenhagen, Denmark. In 11, a Mallory-Weiss syndrome was diagnosed. In 10, the diagnosis was made by means of gastroscopy, and in 1 patient at operation. It was not possible to make the diagnosis by means of X-ray examination of the oesophagus or the stomach. In one patient, a hiatal hernia was found. The etiology was violent and repeated vomiting. In 9 of the cases the syndrome was cuased by chronic alcoholic debauch and migraine. In 1 patient, the disease was caused by an abrupt external trauma of the abdomen after a traffic accident. In the last patient, the cause of the disease was uncertain. The treatment was entirely conservative, i.e. blood replacement, in 10 of the patients. The bleeding stopped after this treatment, and it was not necessary to use a Sengstaken-Blakemore tube, nor was a later surgical exploration needed, except in one patient in whom an emergency operation was required because of extensive and persistent bleeding. At operation, 3 mucosal tears were sutured. At the time of discharge, all 11 patients were feeling well. Based on the present material, and cases reported in the literature, we have concluded that emergency gastroscopy is the most reliable diagnostic measure in patients with the Mallory-Weiss syndrome. The treatment ought to be as conservative as possible with replacement of the blood, and surgical intervention should be performed only in the few patients with incontrollable bleeding.

Adult↗