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Biomedical subjects

W E Hunt

Publications and source records attributed to W E Hunt.

At least 37 records · Page 2Linked to original sources

Crystallographic and molecular-orbital studies on the geometry of antifolate drugs.

In the common dihydrofolate reductase inhibitors an amino substituent replaces the pteridine carbonyl oxygen atom of folates, with altered hydrogen-bonding properties and size. Flexibility in the amino groups could facilitate enzyme binding. Studies of cycloguanil hydrochloride by neutron diffraction show both in-plane and out-of-plane deformation of amino groups. Molecular-orbital calculations ab initio on 2,4-diamino-5-methylpyrimidinium cation confirm that the 4-amino group is readily deformable. The 2,4-diaminoquinazoline structure is reported. Atomic co-ordinates, thermal parameters, bond distances and bond angles for cycloguanil and 2,4-diaminoquinazoline have been deposited as Supplementary Publication SUP 50108 (13 pages) at the British Library Lending Division, Boston Spa. Wetherby, West Yorkshire LS23, 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978) 169, 5.

Chemical Phenomena↗

Cervical spondylosis: natural history and rare indications for surgical decompression.

Degenerative disc disease may be considered a normal process of aging which occurs in virtually the entire population that reaches middle age. Pain problems associated with it should be approached with the greatest reluctance by the surgeon since intermittent flare-ups with subsidence and ultimate overall improvement can be expected in most cases. The clearest indications for surgery have to do with neurologic deficit. The simplest and most obvious example is herniated nucleus pulposus with acute monoradicular or myelopathic symptoms. This situation requires an aggressive approach. More chronic neurologic changes must be approached more cautiously. When unequivocal progression is identified, surgical decompression is in order. Finally, narrowing of the canal from either congenital or acquired processes may in some instances justify prophylactic surgical decompression, but requires the greatest caution. The radiologic findings often do not correlate with the signs and symptoms. The patient's input and his or her full awareness of the possibilities of serious complication is an essential part of good surgical management.

Cervical Vertebrae↗

Carcinoembryonic antigen in cerebrospinal fluid of adult brain-tumor patients.

Carcinoembryonic antigen (CEA) was measured in plasma and cerebrospinal fluid (CSF) in patients with neoplasms and non-neoplastic neurologic conditions of the central nervous system (CNS). Seventy-two control patients had a mean CEAcsf of 0.04 ng/cu cm, 31 patients with benign tumors had a mean CEAcsf of 0.03 ng/cu cm, and 21 patients with malignant CNS tumors had mean CEAcsf of 21.7 ng/cu cm. In the absence of intradural metastasis, the existence of non-CNS malignancies did not cause CEA to appear in the CSF. There was no relationship between the plasma and CSF levels of CEA. The CSF is normally free of CEA, and its detection is strongly suggestive of either primary or secondary intradural malignancy. The titres of CEA decline with effective therapy, and may be of use in monitoring treated patients for recurrence.

Adolescent↗

Impaction fracture of the lumbar vertebrae with dural tear.

The authors described a lumbar spine fracture that is characterized on anteroposterior x-ray views by separation of the pedicular shadows. It is almost invariably associated with posterior interlaminar herniation of the cauda equina through a dorsal dural split, and anterolateral entrapment or amputation of the nerve root. The fracture is unstable and requires internal fixation and fusion at the time of neurolysis. Fractures meeting these criteria should be explored as soon as the patients' condition permits. Myelography is usually unnecessary and may be contraindicated in some cases. The postulated mechanism of injury is hyperextension with vertical impaction and rupture of the ring made up of the lamina, pedicle, and vertebral body. The ring is fractured in several places in a manner similar to that seen in "Jefferson fracture" of C-1. The special anatomical relationships of the thoracolumbar junction and the plane of the lumbar facets are also discussed.

Cauda Equina↗

Platelet aggregation in experimental spinal cord injury. Ultrastructural observations.

Endothelial alterations occur as early as 1 1/2 minutes following impact injury to the primate spinal cord. Separation of the endothelial junctions and exposure of microvascular basal lamina result in platelet adhesion and aggregations that cover defects in the vessel wall and may progress to complete vascular occlusion. This occurs during the first six hours following injury. Platelets also adhere to the surface of damaged endothelium. Hemostasis resulting from platelet thrombus formation is responsible in part for decreased blood flow in the central gray matter following spinal cord trauma.

Animals↗

Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial.

A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.

Adolescent↗

Vasoactive properties of prostaglandin compounds on the in vitro human basilar artery.

The action of six prostaglandins A1, E1, (A2, E2, F1 alpha, F2 alpha) on in vitro human basilar artery circumferential strips was evaluated to assess relative vasoreactivity. Degree of contraction was compared with 5-hydroxytryptamine (5-HT), hitherto the most active in this laboratory. The three most vasoactive prostaglandins were E1, E2, and F2, alpha. The three PGs giving highest magnitude of response were F1 alpha, F2 alpha, and E2. Most were more active when compared to 5-HT. Vasodilation did not occur. Because of their vasoconstrictive qualities, prostaglandins may participate in arterial vasospasm. It is postulated that prolonged vasoconstriction may lead to vasospasm and that the latter may result from one or more autacoids acting along or synergistically.

Basilar Artery↗

Cerebral hemodynamic crisis. Physiology, pathophysiology, and approach to therapy.

The physiology and pathophysiology of the cerebral circulation have been discussed in relation to treatment of the cerebral hemodynamic crisis. Data are presented to show how cerebral vascular resistance, the intracranial compartments, and brain metabolic demand may be manipulated to effect internal decompression and raise local perfusion pressures. It is quite apparent that irreversibility occurs rapidly in cases of complete ischemia and therapeutic success is often limited by this fact. Application of sound therapeutic principles will limit the extent of cellular destruction. Of particular importance to the general surgeon treating the multiply injured patient, is the effect of anesthesia on intracranial pressure in patients with compromised intracranial volume reserve.

Adrenal Cortex Hormones↗

Ultrastructural blood-brain barrier alterations and edema formation in acute spinal cord trauma.

Endothelial changes leading to edema formation are examined in the primate spinal cord (Macaca mulatta) following a lesion created by a 20-gm weight falling 15 cm onto the exposed dura. Intravascular perfusion of a paraformaldehydeglutaraldehyde solution followed by carbon black provides adequate fixation of vascular structures and glial elements. Myelin is poorly preserved. Ultrastructural alterations of the blood-brain barrier consist of loss of integrity of the endothelial tight junctions. Edema caused by vascular disruption and parenchymatous extravasation of intravascular contents is observed along with glial swelling. Interglial gap junctions persist in areas of marked cellular seperation and do not impede the migration of edema fluid.

Animals↗

Tolosa-Hunt syndrome: one cause of painful ophthalmoplegia.

The author reports 12 cases of Tolosa-Hunt syndrome, a benign steroid-resistant cryptogenic granuloma that presents as painful ophthalmoplegia. This syndrome is differentiated from other causes of painful ophthalmoplegia including tumors, aneurysms, collagen disease, specific infections, mucoceles, and benign granulomas of unknown etiology. These other conditions should be excluded by appropriate tests. Surgical exploration is not necessary if there is a prompt remission on steroid therapy.

Adrenal Cortex Hormones↗

Evaluation of mithramycin in the treatment of anaplastic gliomas.

A controlled, prospective, randomized study evaluated the use of mithramycin in the treatment of anaplastic glioma compared to a similar group of patients receiving best conventional care. From a total of 116 patients in the study, 96 were within the valid study group. All patients were operated on, had histological confirmation of anaplastic glioma, and received radiotherapy at the discretion of the principal investigator. Fifty-two patients received mithramycin at a dose of 25 mug/kg/day for 21 days, while 44 patients were in the control group. There was no significant difference in the median survival from time of randomization in those receiving mithramycin (21 weeks) as compared to those not receiving mithramycin (26 weeks). There was no significant difference between the two groups in relation to age distribution, sex, location, diagnosis, tumor characteristics, signs or symptoms, or radiotherapy received. Duration of symptoms correlates positively with survival and was also significantly longer in the control group than in the treated group. This, however, did not account for the failure of mithramycin to be found an effective agent. Although the study was not designed to evaluate the efficacy of radiotherapy, patients who were so treated had a significant improvement in survival. The toxic complications of mithramycin included gastrointestinal symptoms, dermatological involvement, anemia, and liver dysfunction, indicating the need for close supervision.

Adult↗

Postoperative hypertension in the management of patients with intracranial arterial aneurysms.

Elevation of systemic arterial pressure in seven patients with intracranial arterial aneurysms has been shown to be effective in alleviating ischemic symptoms attributed to cerebral vasospasm. Autoregulation is at least partially lost in patients with cerebral hemodynamic crisis. Blood volume expansion was used to augment vasopressors in maintenance of systemic hypertension. The management of these cases is discussed. Caution in the use of this technique is advised, since the regimen is not without risk.

Adolescent↗