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Biomedical subjects

G L Larsen

Publications and source records attributed to G L Larsen.

142 records · Page 8Linked to original sources

Results of treatment of primary carcinoma of the lung. Analysis of 3,000 cases.

Three thousand patients with primary carcinoma of the lung entered in the Armed Forces Central Medical Registry are reported. Forty-one per cent had squamous cell, 28.5 per cent adenocarcinoma, 25.2 per cent small cell/undifferentiated, and 4.9 per cent miscellaneous cell types. When first seen, 71.1 per cent had no organ metastases and 50.6 per cent no lymph node metastases. Over-all survival rate was 18.2 per cent at 5 years and 14.5 per cent at 10 years. Survival following definitive resection, palliative resection, definitive radiation, palliative radiation, and chemotherapy was determined both in the presence of mediastinal nodal involvement and in the absence of mediatinal nodal involvement. Where resection for cure could be carried out, 5 year survival rates of 48.8 per cent were possible. The factors affecting this improved outlook in our military population are discussed and, in general, appear to be related to a ready accessibility of medical care and the necessity, because of global commitments, of establishing an early diagnosis. Cell type ecerted some influence on survival, but the major determinant appeared to be the absence of involved nodes at the time of the operation.

Adenocarcinoma↗

Pyloric stenosis: a 13-year experience in operative management.

Infantile hypertrophic pyloric stenosis is best treated surgically, after an appropriate period of rehydration and resuscitation. Our experience with this entity has resulted in the performance of fewer contrast studies to establish the diagnosis as well as the use of an operative technique which can be safely applied to the teaching environment.

Follow-Up Studies↗

Mediastinoscopy. Its application in central versus peripheral thoracic lesions.

In an attempt to ascertain the value of mediastinoscopy in peripheral lung lesions, records of 157 patients undergoing cervicomediastinal exploration (CME) at Wilford Hall USAF Medical Center were reviewed. Among patients with benign lesions, CME was positive in 90.6% of those who had central lesions and 58.3% of those with peripheral lesions. It was positive in all 7 patients who had peripheral lesions with associated mediastinal nodes on roentgenogram and negative in all 5 who had peripheral lesions without nodes. In the patients with malignant lesions, CME was positive in 72.9% of those who had central lesions and 58.1% of those with peripheral lesions. It was positive in 24 of 27 patients who had peripheral lesions with associated mediastinal nodes and negative in 15 of 16 patients with peripheral lesions without nodes. Although we recognize this to be a selected series, CME does appear to be valuable in patients with central lesions and peripheral lesions with mediastinal nodal involvement on roentgenogram. It does not appear to be as useful in those with peripheral lesions who do not have central nodal involvement.

Adenocarcinoma↗

Identification of NIH-shifted metabolites of 1,3,7,8-tetrachlorodibenzo-p-dioxin in the rat by NMR comparison with synthesized isomers.

In the rat, 1,3,7,8-tetrachlorodibenzo-p-dioxin was oxidatively metabolized to the NIH-shifted products 2-hydroxy-1,4,7,8-tetrachlorodibenzo-p-dioxin and 3-hydroxy-1, 2,7,8-tetrachlorodibenzo-p-dioxin. The chlorine substitution patterns were determined by comparison with 1H NMR spectra of six synthesized isomers in CDCl3, CD3OD, and acetone-d6. Glucuronide and glucuronide-sulfate conjugates of the monohydroxy dioxins were identified in the bile by FAB-MS. The dominance of the NIH-shift products in the metabolism of tetrachlorodibenzo-p-dioxins indicates that the same isomers may be produced from differently substituted chlorinated dioxins.

Animals↗

Metabolism and disposition of 1,4,7,8-tetrachlorodibenzo-p-dioxin in rats.

Metabolism studies of 1,4,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a relatively nontoxic dioxin congener, were undertaken to gain a better understanding of mammalian metabolism of dioxins without the problems associated with the use of the most toxic congener, 2,3,7,8-TCDD. 14C-1,4,7,8-TCDD was dosed to conventional and bile-cannulated rats at a level of 8 mg/kg. The 14C was excreted almost entirely in 72 hours with the major routes of excretion feces and bile. Metabolites were identified from the feces, bile, and urine by GC-MS or negative ion FAB MS and 1H NMR. The two major fecal metabolites were hydroxylated tetra- and triCDDs. Glucuronide and sulfate conjugates of these hydroxyl metabolites were found in the urine and bile. Minor metabolites included dichlorocatechol, dihydroxylated tetra- and triCDDs, and conjugates of these compounds.

Animals↗

An investigation of the binding site of alpha 2u-globulin using isotopically labeled ligands and inverse nuclear magnetic resonance techniques.

A series of isotopically labeled ligands were bound to the protein alpha 2u-globulin. These protein complexes were studied using 13C, 19F, and selective inverse detection NMR experiments to determine chemical shifts and nuclear Overhauser effect correlations for the labeled sites of the ligands. The NMR data indicate that the labeled portions of the ligands are located in a highly aromatic region of the alpha 2u-globulin binding pocket. Molecular modeling based on the NMR data and a medium resolution X-ray crystal structure of alpha 2u-globulin predicts a model for ligand binding which is consistent with experimental observations and calculated ring current effects. Conformational changes in the aromatic region of the binding site upon binding these ligands in solution may be supported by this model.

Alpha-Globulins↗

Enterohepatic circulation of the mercapturic acid and cysteine conjugates of propachlor.

Germfree (GF) rats and antibiotic-treated rats with cannulated bile ducts (ABC) were given single oral doses of 2-(S-(N-[2H3]acetyl)cysteine)-N-isopropyl[1-14C]acetanilide. The GF rats excreted the dose in about equal quantities in the urine and feces; and the ABC rats excreted the dose in about equal quantities in the urine, feces, and bile. The mercapturate (60-75% of the dose in both cases) was isolated and the amount of exchange of N-acetyl deuterium to N-acetyl hydrogen was determined for all samples by mass spectrometry. The percentages of exchange were: ABC rats, bile 6.5%, urine 13%, feces 0.0%; GF rats, urine 15%, feces 4.7%. The remainder of the doses was present as the mercapturic acid sulfoxide. ABC rats dosed with 2-(S-[3,3-3H]cysteine)-N-isopropyl[1-14C]acetanilide (14C/3H = 0.50) excreted 42% of the dose in the urine and bile as the mercapturic acid that had a 14C/3H ratio the same as the original cysteine conjugate. The results of these studies show that a mercapturic acid and a cysteine conjugate can be absorbed from the gastrointestinal tract and resecreted in the bile or excreted by the kidney without having undergone metabolism other than acetylation of the cysteine nitrogen atom and oxidation of the sulfur to a sulfoxide. ABC rats were also dosed with 2-methylthio-N-isopropyl[1-14C]acetanilide, a suspected metabolic intermediate in the metabolism of propachlor (2-chloro-N-isopropylacetanilide). The dose was excreted in about equal quantities in the bile (48%) and urine (46%) as metabolites with a methylsulfonyl group in the 2-position. All are known metabolites of propachlor in conventional rats.

Acetanilides↗