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Biomedical subjects

J L Fox

Publications and source records attributed to J L Fox.

At least 19 recordsLinked to original sources
PubMed1979

Physical model evaluation of topical prodrug delivery-simultaneous transport and bioconversion of vidarabine-5'-valerate I: Physical model development.

A physical model approach to the topical delivery of a vidarabine ester prodrug was investigated. It involved modeling, theoretical simulations, experimental method development for factoring and quantifying parameters, and, finally, employment of the deduced parameters to determine the steady-state species fluxes and concentration profiles in the target tissue. The present report describes the physical modeling and theoretical simulation aspects. The physical model for the simultaneous transport and bioconversion of a topically delivered prodrug was formulated assuming homogeneous enzyme distributions and constant diffusivities in the membrane. The mathematical problem was solved, and the solution yielded concentration profiles and fluxes of all species in the biomembrane. These results provided the prevailing levels of the prodrug, the drug, and the metabolite at the target site and the transport rates of all species into the bloodstream. Computations of concentration profiles and fluxes were carried out for a reasonable range of the parameters. The relative activities of the esterase and the deaminase enzymes, as well as the stratum corneum permeabilities, were important in influencing the concentration profiles and fluxes of all species.

Administration, Topical↗
PubMed1979

Physical model evaluation of topical prodrug delivery-simultaneous transport and bioconversion of vidarabine-5'-valerate II: Parameter determinations.

Results of initial studies on methods for determining various model parameters are reported. By employing excised hairless mouse skin in a diffusion cell system, numerous model parameter values were deduced. The stratum corneum permeability was estimated from steadystate fluxes with preparations of heat-separated epidermal membranes. Determinations of dermis diffusivities and enzyme rate constants in situ involved considering the simultaneous transport and the enzyme processes and factoring the diffusivities and enzyme rate constants from the overall kinetics. Dermal diffusivities were on the order of 10-6 cm2/sec for vidarabine and its 5'-valerate ester. The enzyme rate constants were 1.70 x 10-3 sec-1 for the esterase and 8.68 x 10-3 sec-1 for the deaminase.

Animals↗
PubMed1979

Neurogenic bladder and the tethered spinal cord syndrome.

We report 2 cases of the tethered spinal cord syndrome. Early clinical detection of this syndrome in children with bladder dysfunction should be followed by diagnostic myelography and immediate surgical release of the spinal cord. The pathophysiology of the syndrome is discussed.

Child↗
PubMed1979

Intracranial vasospasm: a study with iron compounds.

The effects of topically applied hemoglobin, methemoglobin, hemin, ferrous chloride (FeCl2) and ferric chloride (FeCl3) were investigated by observation through the operating microscope to determine their effect on the normal and spastic canine basilar artery. Following transclival exposure, the artery was made spastic by puncture or topical barium chloride. No consistent changes in arterial diameter were seen with topical hemoglobin, methemoglobin, or hemin. The buffered ferrous ion (Fe++) caused marked vasodilation at concentrations of 10 microgram/ml. The buffered ferric ion (Fe++) caused mild vasoconstriction at similar concentrations. The possible role of iron (a component of hemoglobin) in vasospasm following subarachnoid hemorrhage and subsequent hemoglobin degradation is discussed.

Animals↗
PubMed1979

Multiple giant aneurysms.

A case with four unusual aneurysms is presented. On the right were a ruptured small middle cerebral artery aneurysm and a giant carotid-ophthalmic artery aneurysm. On the left were two giant internal carotid artery aneurysms: one at the ophthalmic artery and one at a ventral or paraclinoid position. All four aneurysms were clipped. The patient returned to her household duties.

Carotid Artery Diseases↗
PubMed1978

The evolution of protein sequences by repetitious gene duplication: clostridial flavodoxin.

Internal regularities of amino acid sequences of flavodoxins, FMN-containing, low molecular weight flavoproteins, were statistically examined using the minimum mutation method. The sequence of Clostridium pasteurianum flavodoxin shows statistically significant evidence of repetitious internal gene duplications at different levels of structure. Peptide pairs with a low chance probabilitiy of occurrence were frequently observed at a shift of 5 residues. The pairs with the lowest chance probabilities are a pair of heptapeptides at positions39--45 vs. 44--50, a 5 residue shift (p = 9 x 10(-6)). Most of the related pairs are consistent and could best be explained by the repeating pentapeptide sequence: (Lys-Gly-Ala-Asp-Val-)n and appropriate gaps. Internal repetitions with longer shifts were also suggested for other flavodoxins. Repetitious gene duplication is proposed for the early stages of flavodoxin evolution.

Amino Acid Sequence↗
PubMed1978

Cerebral vasospasm: a clinical observation.

Three cases of subarachnoid hemorrhage from intracranial aneurysms are presented. Two of the patients survived long enough to develop delayed cerebral vasospasm. The computerized tomograms and angiograms were correlated with the clinical course. It is suggested that delayed cerebral vasospasm may be preceded by relative vasodilation, or at least inhibition of vasocontraction, and concomitant increased vascular permeability of the parent vessels diagnosed by contrast enhanced computerized tomography. This phenomenon, if confirmed in larger series of patients, may allow prediction of that patient destined for vasospasm and may suggest some of the pathophysiology of this devastating problem.

Adult↗
PubMed1977

Amino acid sequence of Desulfovibrio vulgaris flavodoxin.

The complete amino acid sequence for the 148-amino acid flavodoxin from Desulfovibrio vulgaris was determined to be: H3N+-Met-Pro-Lys-Ala-Leu-Ile-Val-Tyr-Gly-Ser-Thr-Thr-Gly-Asn-Thr-Glu-Tyr-Thr-Ala-Glu-Thr-Ile-Ala-Arg-Glu-Leu-Ala-Asn-Ala-Gly-Tyr-Glu-Val-Asp-Ser-Arg-Asp-Ala-Ala-Ser-Val-Glu-Ala-Gly-Gly-Leu-Phe-Glu-Gly-Phe-Asp-Leu-Val-Leu-Leu-Gly-Cys-Ser-Thr-Trp-Gly-Asp-Asp-Ser-Ile-Glu-Leu-Gln-Asp-Asp-Phe-Ile-Pro-Leu-Phe-Asp-Ser-Leu-Glu-Glu-Thr-Gly-Ala-Gln-Gly-Arg-Lys-Val-Ala-Cys-Phe-Gly-Cys-Gly-Asp-Ser-Ser-Tyr-Glu-Tyr-Phe-Cys-Gly-Ala-Val-Asp-Ala-IleGlu-Glu-Lys-Leu-Lys-Asn-Leu-Gly-Ala-Glu-Ile-Val-Gln-Asp-Gly-Leu-Arg-Ile-Asp-Gly-Asp-Pro-Arg-Ala-Ala-Arg-Asp-Asp-Ile-Val-Gly-Try-Ala-His-Asp-Val-Arg-Gly-Ala-Ile-COO. This protein is of interest as it was the first flavoenzyme for which high resolution x-ray diffraction studies were published (Watenpaugh, K.D., Sieker, L.C., and Jensen, L.H. (1973) Proc. NAtl. Acad. Sci. U.S.A. 70, 3857-3860). Ser(10), Thr(12), Asn(14), and Thr(15) were shown to bind the phosphate of the FMN while the isoalloxazine ring is positioned between Trp(60) and Tyr(98).

Amino Acid Sequence↗
PubMed1977

An unusual atlanto-axial dislocation. Case report.

A case is presented in which the patient sustained a complete dislocation of the odontoid process in front of the anterior arch of the first cervical vertebra. There was no fracture of the arch of C-1 vertebra. The patient was treated successfully by trans-oral excision of the odontoid process and the anterior arch of C-1. Twenty days later the patient's spine was stabilized posteriorly at C-1 through C-3 with wire and methyl-methacrylate.

Aged↗
PubMed1977

Effects of procainamide and chloramphenicol on acute vasospasm.

The basilar artery of the dog was exposed through the clivus and made spastic by puncture or by topical application of 5% barium chloride. Injections of procainamide or chloramphenicol into the vertebral artery or into a peripheral vein had no discernable effect on the acute vasospasm. Topical application of 0.1% to 10% concentrations of either of these drugs effected definite vasodilation, with the extent and rapidity of vasodilation increasing with increasing concentrations. Lesser concentrations were ineffective.

Acute Disease↗
PubMed1977

Automatic cycling bipolar coagulator.

Bipolar coagulation may be more effective if the currents is delivered in short bursts. This technique is described, along with a bipolar coagulator which automatically dispenses the current in short regularly cycled bursts.

Electrocoagulation↗