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Biomedical subjects

L Frohman

Publications and source records attributed to L Frohman.

27 records · Page 2Linked to original sources

Solution structures of cyclic and dicyclic analogues of growth hormone releasing factor as determined by two-dimensional NMR and CD spectroscopies and constrained molecular dynamics.

Solution structures were determined for a linear analogue of growth hormone releasing factor (GRF), and cyclic and dicyclic analogues in which the side chains of aspartyl and lysyl residues spaced at positions i-(i + 4) were joined to form a lactam. The four analogues were [Ala15]-GRF-(1-29)-NH2 and its cyclo8-12, cyclo21-25, and dicyclo8-12;21-25 derivatives. The peptides were studied in two solvent systems: 75% methanol/25% water at pH 6.0; and 100% water at pH 3.0. CD spectroscopy was used to assess the overall alpha-helical content. Nuclear magnetic resonance spectroscopy was used to determine the structures in more detail. Nearly complete proton resonance assignments were made for each of the peptides, in both solvents. Nuclear Overhauser effects were converted into distance constraints and applied in the molecular dynamics program CHARMM to evaluate the range of low-energy structures that satisfied the nmr data. In 75% methanol, all of the peptides are comprised of a single alpha-helical segment with fraying of one to three residues at each end. The linear analogue has a tendency to kink. In water, the analogues have two helical segments with flexible regions between them and at the termini of the peptides. The linear analogue is helical at residues 7-14 and 21-28. In the cyclo8-12 analogue, the N-terminal helical region extends to include residues 7-19, while the other helical region is slightly shortened. In the cyclo21-25 analogue, the C-terminal helical region is extended to include residues 19-28, while the N-terminal helical region is destabilized. The dicyclic analogue has the largest N-terminal helix, spanning residues 7-20, but its helical segment at residues 21-28 is not well ordered. All of the analogues exhibit substantial biological activity. The cyclic and dicyclic analogues show dramatically increased resistance to degradation during incubation with human plasma. The i-(i + 4) lactam, therefore, appears to be a synthetic means of stabilizing a local alpha-helical conformation, which may be of general use in the design of active, stable peptides.

Amino Acid Sequence↗

Management of traumatic optic neuropathy--a study of 23 patients.

Twenty three patients with traumatic optic neuropathy were managed by medical and surgical treatment as follows. High dose intravenous steroids were initiated in all patients. If visions did not improve significantly after 24 to 48 hours decompression of an optic nerve sheath haematoma by medial orbitotomy and neurosurgical decompression of the optic canal were considered based on computed tomographic scan findings. Nine of 16 patients who received steroids only showed significant improvement. One of three showed improvement on optic nerve decompression after steroid failure; three or four showed improvement on optic nerve decompression after steroid failure; three or four showed improvement with combined optic nerve sheath decompression by the medial orbitotomy and decompression of the optic canal by frontal craniotomy. A lucid interval of vision after injury and an enlarged optic nerve sheath were associated with an improved prognosis. Five of the 23 patients had a lucid interval and all five had a final improved vision, while only five of 18 patients without a lucid interval improved. Similarly seven of the nine with an enlarged optic nerve sheath showed improvement while only three of 10 patients (three bilateral cases) who presented with no light perception improved with medical and surgical treatment. While a prospective controlled study of the management of traumatic optic neuropathy is necessary this preliminary study suggests that treatment of traumatic optic nerve sheath haematoma by optic nerve sheath decompression should be considered in selected patients.

Adolescent↗

Thyroid scintigram. Sensitivity with sodium pertechnetate Tc 99m and gamma camera with pinhole collimator.

To evaluate the reliability of thyroid scintigraphy in the diagnosis of nodular growth, scintigrams of patients who later underwent thyroidectomy were reviewed and correlated with pathologic findings. The scintigrams were all obtained with a 5-mm single-hole collimator-equipped gamma-scintillation camera after intravenous injection of 5 millicuries of sodium pertechnetate Tc 99m. In the group of 92 patients, six of whom had two histologically different lesions, 149 nodules were identified pathologically. There were 26 nodules 2 to 5 mm in diameter, of which 22 were benign and four were malignant. None of the 22 benign nodules were delineated scintigraphically. Superior image quality and resolution, low radiation dose, technical simplicity, and speed make 99mTc pinhole-camera scintigraphy the best procedure available for routine thyroid imaging.

Adenocarcinoma↗

99mTc-pertechnetate thyroid scintigraphy in patients predisposed to thyroid neoplasms by prior radiotherapy to the head and neck.

Histories, physical examinations and 99mTc-pertechnetate imaging were used to evaluate 1,452 persons who had had x-ray therapy to the neck region for benign conditions 18 to 35 years previously. Thyroid abnormalities were found in 301 patients (21%) and thyroid malignancy was found in 29% of 193 patients with abnormal studies who were explored surgically. Thyroid imaging detected 96% of these abnormalities, 40% of which would not have been unequivocally established by physical examination alone. Nuclear imaging could not distinguish benign from malignant lesions.

Adenocarcinoma↗

Sudden painless visual loss.

Common signs and symptoms of temporal arteritis include headache, scalp tenderness, jaw claudication, anemia, and an elevated sedimentation rate (ESR). Severe complications can include blindness, retinal artery occlusion, and optic neuropathy. While temporal arteritis may be suggested by patient history, other causes that can mimic its presentation must be considered, especially when visual loss occurs in the setting of a normal funduscopic exam. We report a case of invasive sino-orbital aspergillosis that mimicked the clinical signs and symptoms typically associated with temporal arteritis. A high index of suspicion and appropriate radiological and laboratory studies prevented delays in formulating the correct diagnosis and treatment plan.

Aged↗