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Biomedical subjects

G E Shambaugh

Publications and source records attributed to G E Shambaugh.

At least 73 records · Page 4Linked to original sources
PubMed1982

Ultrastructural analysis of endolymphatic sac biopsies. Biopsy technique and identification of endolympathic sac epithelium.

This study describes the technique and instrumentation necessary to perform a double-wall biopsy of the endolymphatic sac (ELS). Since this technique protects the lumen of the ELS, which is within the center of the biopsy sample surrounded by the lateral and medial wall, the ultrastructure of the ELS epithelium, luminal contents, and perisaccular connective tissue tends to represent the in vivo status. The biopsy specimen can be analyzed by electron microscopy for clinical-pathologic correlation. Ultrastructural analysis (1) provides definite identification of the ELS and epithelium, (2) may provide insight into a possible role of the ELS in the pathogenesis of endolymphatic hydrops, and (3) can provide much improved clinical-pathologic correlation over only light microscopic studies.

Biopsy↗
PubMed1982

Fetal fuels. V. Ketone bodies inhibit pyrimidine biosynthesis in fetal rat brain.

Ketonemic states complicating late pregnancy are accompanied by lower brain weights in the newborn. Potential mechanisms whereby ketone bodies might inhibit cell proliferation were therefore examined in the fetal rat brain slice by measuring their impact on the de novo pathway for pyrimidine biosynthesis. DL-beta-hydroxybutyrate (10.8 mM) and acetoacetate (5.4 mM) were both found to diminish the incorporation of NaH14CO3 into [14C]UMP by 30%. This effect was similar in fetal tissues from fed and 48-h starved mothers. Graded concentrations of DL-beta-hydroxybutyrate (1.4-43.2 mM) resulted in a progressive inhibition that could not be explained either by isotope dilution consequent to ketone body oxidation or by a generalized inhibition of protein synthesis. The inhibition was not reversed with 10 mM glutamine, the principal nitrogen substrate for de novo biosynthesis of pyrimidines. When the conversion of orotic acid into UMP was blocked with 6-azauridine, DL-beta-hydroxybutyrate (10.8 mM) inhibited the incorporation of NaH14CO3 into orotic acid by 28%. By contrast, maximally inhibitory concentrations of this ketone body (43.2 mM) had no effect on the incorporation of [6-14C]orotic acid into [14C]UMP. Is is concluded that ketone bodies inhibit the de novo biosynthesis of pyrimidines in fetal brain slices and that they do so at a site proximal to orotic acid formation.

Animals↗
PubMed1982

The enzymatic mechanism of the otospongiotic disease and NaF action on the enzymatic balance.

Extensive research on enzymes led to the discovery of the innermost mechanism of the otospongiotic disease. The authors present the results of multiple correlations made from February 1976 to September 1980 on 648 samples of perilymph taken during stapedectomies performed on otosclerotic patients. We studied microdosages of three selected enzymes--trypsin, alpha 1 antitrypsin, and alpha 2 macroglobulin--in each of the samples and their relationship with cochlear deterioration expressed in dBs of bone conduction decrease in pure-tone audiometry testing. This study allowed us a better knowledge of the enzymatic mechanism of the otospongiotic disease, based on the previously reported trypsin-alpha 1 antitrypsin balance, but in which alpha 2 macroglobulin appears to play a role as essential as that of alpha 1 antitrypsin. This enzymatic mechanism explains NaF efficiency, which is due in fact to a double action: not only direct trypsin inhibition, but also an overall reduction in enzymatic values in the perilymph of otospongiotic/otosclerotic patients. Current studies could lead to the possibility of future NaF replacement by proteinase inhibitors either of microbial origin, under study by Japanese researchers, or even of synthetic origin, which should be investigated. In fact, the role of NaF therapy could already be taken over by diphosphonates currently under study.

Audiometry, Pure-Tone↗
PubMed1981

Fetal fuels. IV. Regulation of branched-chain amino and keto acid metabolism in fetal brain.

The regulation of branched-chain amino and keto acid metabolism was examined in fetal rat brains at 20 days gestation. When fetal brain slices were incubated with [1-14C]leucine, graded concentrations of beta-hydroxybutyrate or acetoacetate resulted in a progressive rise in labeled alpha-ketoisocaproic acid accompanied by a fall in 14CO2, whereas the sum of these products remained unchanged. These reciprocal relationships were maintained when leucine concentrations were varied from 0.4 to 4 mM. Increasing concentrations of glucose or pyruvate enhanced the formation of both 14CO2 and alpha-ketoisocaproic acid from [1-14C]leucine, but resulted in a progressive decrease in the conversion of alpha-ketoisocaproic acid to 14CO2. That glucose and ketone bodies probably acted via separate mechanisms was suggested by a further inhibition of alpha-ketoisocaproic acid decarboxylation whenever beta-hydroxybutyrate was added. When mothers were starved from days 18-20, a threefold rise in circulating branched-chain keto acids was reflected concordantly in the fetus and was attended by a significant enhancement of leucine transaminase activity in fetal brain. Because levels of circulating ketone bodies reported during maternal starvation were maximally effective in diminishing the conversion of alpha-ketoisocaproic acid to 14CO4, it is suggested that the inhibitory effects of beta-hydroxybutyrate on the critical dehydrogenase step in branched-chain keto acid metabolism in fetal brain could restrain oxidation of maternally derived alpha-ketoisocaproic acid, thereby permitting salvage for reversible transamination to leucine.

3-Hydroxybutyric Acid↗
PubMed1981

An holistic approach to Ménière's disease. Medical and surgical management.

A review of the medical and surgical management of 195 patients with Meniere's disease is presented. In order to avoid a piecemeal approach to the problem of Meniere's disease, the "whole" patient must be treated. Psychological counseling, medical management, and when indicated selective surgical management is advocated. The diagnosis of Meniere's must be confirmed through careful history, physical, neurological evaluation and selective testing. The majority of patients can be controlled medically; however, in this study 52 (26%) patients underwent surgical therapy. Twenty-eight patients underwent some type of saccus surgery for Meniere's disease with overall relief of 71%; however, better relief of vertigo was seen with labyrinthectomy and nerve section. The most common indication for surgery was disabling vertigo. However, fluctuating progressive sensorineural loss, may be an important reason to advise surgery. Surgical techniques for Meniere's disease continue to evolve. A graduated approach is preferred, starting with endolymphatic-mastoid shunt, proceeding to middle fossa vestibular nerve section when medical status and hearing and adequate. When hearing is socially inadequate, labyrinthectomy with or without vestibular nerve section is preferred. A good working relationship with a neurosurgeon is advised for otolaryngologists performing middle fossa surgery.

Counseling↗
PubMed1980

Effect of fluoride on alpha-chymotrypsin.

Sodium fluoride has been demonstrated by spectrophotometric experiment to have an inhibitory effect on the hydrolyzing action of alpha-chymotrypsin. Sodium fluoride in moderate therapeutic dosage possibly can retard or completely inhibit the activity of bone-resorbing enzymes in the otospongiotic focus, thus retarding or arresting active expansion of a focus and resulting in stabilizing or arresting the progression of sensorineural hearing loss that is associated with otospongiosis.

Chymotrypsin↗
PubMed1980

Glucose metabolism in uremia.

Formation of CO2 from uniformly labeled 14C-glucose was measured in liver slices from uremic and normal rats. Both CO2 formation and lactate concentration were decreased in the uremic liver slices suggesting an inhibition of glucose oxidation. In addition, a net loss of glucose from the medium in the uremic preparation and a net gain in the normal controls suggested that there was increased nonoxidative utilization in the uremic liver. Such changes could not be explained by differences in glucose availability consequent to alterations in glycogen degradation. The most likely explanation is diversion of glucose into other biosynthetic pathways such as the synthesis of amino acids. In this regard, synthesis of glutamine appeared to be enhanced in uremia. Thus, products of carbohydrate metabolism may provide a potential mechanism for disposition of ammonia and synthesis of amino acids in uremia.

Animals↗
PubMed1980

Effects of prestimulatory carbogen inhalation on noise-induced temporary threshold shifts in humans and chinchilla.

Human subjects and chinchilla breathed either Carbogen or compressed air prior to high level sound stimulation. Following stimulation, threshold shifts and recovery to prestimulation thresholds were monitored. Behavioral audiometry was used for human subjects and electrocochleography was utilized to measure noise-induced threshold shifts in the animals. Results were similar for both human and animal subjects in that preinhalation of Carbogen (05 percent 02 and 5 percent CO2) was seen to decrease the amount of temporary threshold shift (TTS) and to increase recovery rate. Further, histologic study of a limited sample of the experimental animals suggested a notable reduction in the amount of sensory cell damage in subjects that breathed Carbogen before sound stimulation. To follow up on this encouraging indication, an additional experiment was conducted to investigate any differences between Carbogen-treated and non-Carbogen-treated animals with respect to histologically observable high level noise exposure damage. The follow-up experiment resulted in strong evidence that Carbogen inhalation prior to intense sound stimulation decreases the susceptibility to hair cell damage. Carbogen-treated chinchilla sustained cochlear sensory cell damage ranging between 1.1 percent and 1.5 percent, whereas non-Carbogen-treated, noise-exposed chinchilla were found to have between 1.6 percent and 4.6 percent sensory cell damage. The use of Carbogen in prophylactic treatment for unavoidable or accidental noise exposure is discussed.

Acoustic Stimulation↗
PubMed1979

Endolymphatic sac valve implant surgery. I: The technique.

A resurgence of interest in surgery on the endolymphatic sac (ELS), not only for relief of vertigo but also for stabilization or improvement of hearing, has emerged. With the concept of operating early in the course of the disease after the diagnosis is well established, various modifications of existing procedures on the ELS have been utilized in an attempt to improve the overall results. One such major modification is the unidirectional inner ear valve implant modified from the eye valve for glaucoma. This valve implant has produced impressive one-year results for both hearing improvements and relief of vertigo in patients who were scheduled for labyrinthectomy. Subsequent preliminary reports by several investigators show good to excellent results for the hearing (AAOO--Class B or A) as well as the vertigo without consideration for the stage of the disease. This study presents primarily the step by step technique with drawings and a color atlas to facilitate the correct performance of this surgery.

Ear, Inner↗