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Intranasal corticosteroid injection: indications, technique, and complications.

The intranasal injection of corticosteroids for symptomatic relief of nasal obstruction in selected cases has been described by several authors and widely used for over 25 years. Recently, circulated reports of blindness following such injections caused a number of otolaryngologists to discontinue using the procedure. All reported cases of visual complications following intranasal corticosteroid injection are reviewed, together with the reported experiences of the author and others who have successfully used the technique in thousands of cases. Preliminary topical cocainization of nasal mucosa and slow submucosal injection of a micronized corticosteroid suspension to minimize the risk of vasospasm and embolization involving the ophthalmic circulation are stressed. Indications for the procedure, the most common side effects, and the proper technique of injection are described.

Administration, Intranasal↗
PubMed1979

Macrophage-dependent, NK-cell-independent "natural" surveillance of tumors in syngeneic mice.

The present study, which was designed to further characterize the "natural" T-independent rejection of syngenetic tumours (Greenberg and Greene, 1976), has revealed the following points: (1) no detectable DBA/2 NK cell activity was demonstrated against the syngeneic tumour lines studied, and these tumours were indensitive to NK cells from high-activity strains; (2) in addition the tumour frequencies in old and young mice receiving small tumour inocula were identical, in contrast with the reported decline in NK cell activity with age, suggesting that the surveillance of small inocula of these tumours was NK-cell-independent; (3) injection of silica intraperitoneally enhanced the frequency of tumours in normal and immunodeficient AT x BM mice, suggesting that the rejection mechanism was macrophage-dependent; (4) the effects of silica injection were maximal if administered 3 days prior to tumour injection, indicating that the period of time in which the rejection mechanism must act was very limited; (5) silica markedly decreased the survival of AKR mice dying of spontaneous tumours, providing evidence that the effect of this agent was not limited to model systems but would influence the appearance of spontaneous tumours; (6) reticuloendothelial stimulants such as mycobacterium butyricum and proteose peptone decreased the tumour frequency of small tumour inocula, indicating that the effector mechanism can be stimulated; and (7) soluble tumour antigen enhanced the tumour frequency in normal and immunodeficient mice, suggesting that the specific receptor molecule of the surveillance mechanism was not thymus-dependent.

Animals↗
PubMed1978

Axonal transport of lipid in goldfish optic axons.

After injection of labeled glycerol, choline, or serine into the eye of goldfish, labeled lipids were axonally transported along the optic nerve to the optic tectum. Although the different precursors were presumably incorporated into somewhat different lipid populations, all three were approximately equally effective in labeling the lipids transported to the tectum, but the amount of transported material remaining in the nerve was different, being highest with choline and lowest with serine. The labeled lipids appeared in the tectum within 6 hr of the injection, indicating a fast rate of transport, but continued to accumulate over a period of 1--2 weeks, which presumably reflects the time course of their release from the cell body. Since there was a gradual increase in the proportion of labeled lipid in the tectum during this period, some other process in addition to fast axonal transport may have affected the distribution of the lipids along the optic axons. When [3H]choline was used as precursor, the transported material included a small amount of TCA-soluble material, which was probably mainly phosphorylcholine, with labeled acetylcholine appearing in only insignificant amounts. With serine, which gave rise to a large amount of axonally transported protein in addition to lipid, a late increase in the amount of labeled lipid in the tectum was seen, accompanied by a decrease in labeling of the protein fraction.

Acetylcholine↗
PubMed1978

The use of kainic acid in the localization of enzymes in the substantia nigra.

The selective destruction of neuronal perikarya via intracerebral injections of kainic acid was used to elucidate the cellular location of four neurotransmitter-related enzymes in the substantia nigra (SN). Two weeks after intranigral injections of kainic acid, dopamine-sensitive adenylate cyclase, glutamic acid decarboxylase (GAD), choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were measured in the SN. Histological examination of the SN, and a reduction of striatal tyrosine hydroxylase (TH) activity by 94%, confirmed the extensive loss of neuronal cell bodies in the SN. Dopamine stimulation of adenylate cyclase was not reduced in the lesioned SN, supporting the view that dendritically-released dopamine can regulate cyclic AMP synthesis in afferent terminals to these dendrites. Nigral GAD activity was significantly reduced by the lesions, suggesting that there are GAD-containing perikarya in the SN. CAT activity was not affected by the kainic injections, indicating the absence of cholinergic perikarya in the SN. Nigral AChE activity was significantly decreased after kainic injections, thus confirming the presence of AChE within the nigral perikarya. The results suggest that dopamine-sensitive adenylate cyclase and CAT are located within afferents to the SN, while GAD and AChE are found, to some extent at least, in neuronal soma of the SN. The differentail effects of kainic acid on these enzymes suggest that this compound may be a useful neurochemical tool with which to determine the cellular distribution of enzyme systems in the central nervous system.

Acetylcholinesterase↗
PubMed1979

Axonal transport and metabolism of [3H]fucose- and [35S]-sulfate-labeled macromolecules in the rat visual system.

The axonal transport of labeled macromolecules in retinal ganglion cells of rats was investigated from 1 to 20 days following intraocular injection of [3H]fucose and [35S]sulfate. Maximal incorporation of [3H]fucose into acid insoluble material in the retina was at 8 h, followed by a biphasic decline. Transported [3H]fucose (98% as glycoprotein) was in the optic nerve at 1 h, the optic tract and lateral geniculate body by 2 h, and the superior colliculus by 3 h after injection, indicating a rate of transport of approximately 200 mm/day. Radioactivity continued to accumulate in the superior colliculus for at least 8 h and began to decline rapidly by 24 h. Between 3 and 6 days levels rose again in both optic tract and superior colliculus before starting a gradual decline, indicating that a wave of rapidly transported material was delayed in leaving the retina. When proteins in the superior colliculus were fractionated by gel electrophoresis, the composition of the two fucosylated protein transport phases could be partially resolved. Radioactivity in individual gel peaks represented primarily in the first phase decayed with an average half-life of one day, althouth that in one prominent protein of molecular weight 280,000 turned over with a half-life of the order of 12 h. Radioactive peaks primarily in the second phase decayed with an average half-life of more than a week. Incorporation of [35S]sulfate into acid insoluble material in the retina was maximal at 1-2 h, after which there was a rapid loss of label. The appearance of [35S]sulfate in the optic tract, lateral geniculate body and superior colliculus preceded by a short time that of the [3H]fucose; indicating a shorter retinal processing time for this label. The total transported [35S]sulfate in the superior colliculus peaked by 4-8 h and had fallen by 65% at one day; no prominent second wave of transport was observed as was the case for [3H]fucose. Acid insoluble [35S]sulfate in the superior colliculus was equally divided between glycopeptides and glycosaminoglycans at all times examined, indicating that these macromolecules are transported at the same rate. [35S]Sulfate incorporated into various proteins fractionated by gel electrophoresis had heterogeneous turnover rates, the average being around 12 h. Radioactivity in one group of proteins, of molecular weight around 90,000, decayed with a half-life of only a few hours.

Animals↗
PubMed1977

In vivo repair of rat liver DNA damaged by dimethylnitrosamine or diethylnitrosamine.

Effects of hepatocarcinogens dimethylnitrosamine (DMN) and diethylnitrosamine (DEN) on the sedimentation pattern of rat liver DNA in alkaline sucrose gradients were studied with regard to time and dose dependency. Both DMN (10 mg/kg body weight) and den (13.4 or 134 mg/kg) induced appreciably decreased DNA sedimentation rates at 24 h after injection. DMN at 10 mg/kg was as effective in decreasing the DNA sedimentation rate at 24 h after injection as was the higher dose of DEN (134 mg/kg). Sedimentation patterns at 1, 6 and 14 days after injection indicated that damage induced by DEN (134 mg/kg) was repaired at a substantially lower rate than DMN (10 mg/kg) induced damage. When effects of equimolar doses of DMN (10 mg/kg) and DEN (13.4 mg/kg) were compared at 1, 6 and 14 days after injection, it was observed that the more pronounced damage of rat liver DNA induced by DMN was repaired at a faster rate than was the DEN-induced damage. At the molecular level this difference in repair between damage induced by the two nitrosamines is probably related to different DNA alkylation patterns. The relatively persistent nitrosamine-induced DNA lesions (observed especially after DEN administration) are thought to represent phosphotriesters which give rise to single strand DNA breaks at strongly alkaline conditions of lysis on top of the gradient. The results are discussed in relation to the possible significance of alkylation and repair of DNA in the formation of (pre)cancerous lesions in rat liver.

Alkylation↗
PubMed1979

Turnover of prolyl hydroxylase tetramers and the monomer-size protein in chick-embryo cartilaginous bone and lung in vivo.

The turnover of prolyl hydroxylase and an immunoreactive protein that corresponds in size to the smaller subunit of the enzyme was studied in vivo after injection of [(3)H]leucine into 11-day chick embryos. The specific radioactivity and total radioactivity of the monomer-size protein were much higher than those of the enzyme tetramers in the cartilaginous bone at 3h and 12h after the radioisotope injection, indicating that the monomer-size protein represents precursors rather than degradation products of the enzyme tetramers. Between 24 and 144h after the injection the specific radioactivity and total radioactivity of the two forms of the enzyme protein showed essentially identical decay rates, the observed specific radioactivity of the monomer-size protein being about 120-130% and total radioactivity about 80% of that of the enzyme tetramers. The true half-life, when corrected for dilution caused by tissue growth and re-utilization of the [(3)H]leucine, was 37.9h for the monomer-size protein and 39.0h for the tetramers. The results obtained in the lung were less reliable owing to high blank radioactivity values in the immunoprecipitation, but even so some definite differences were found between this tissue and the cartilaginous bone. The specific radioactivity of both forms of the enzyme protein at 24h was only about 20-25% of that in the cartilaginous bone. The total radioactivity of the monomer-size protein in the lung remained about 5 times that of the enzyme tetramers, whereas it was only about 0.8 times that of the tetramers in the cartilaginous bone. As in the cartilaginous bone, the decay rates of both forms of the enzyme protein were essentially identical in the lung, with a true half-life of about 46h. The results suggest that the rate of prolyl hydroxylase synthesis is slower in the lung than in the cartilaginous bone, whereas the degradation rates are fairly similar in these two tissues. The data further suggest that, in the lung at least, a large part of the monomer-size protein became degraded without being converted into enzyme tetramers.

Animals↗
PubMed1975

The effect of reserpine on hypothalamo-pituitary-adrenocortical function in the rat.

1. The effect of reserpine on hypothalamo-pituitary-adrenocortical (HPA) function in the rat was investigated by the use of direct and indirect indices of pituitary adrenocorticotrophic activity. 2. Administration of a single dose of the drug induced prolonged hypersecretion of corticotrophin (ACTH). 3. Corticotrophin release in response to the drug no longer occurred after repeated daily injections, indicating that some form of 'adaptation' occurred. 4. The increase in HPA activity normally caused by exposure to cold was prevented by reserpine once 'adaptation' to the drug had been produced. 5. Inhibition of stress-induced ACTH release was due neither to depletion of pituitary stores of the hormone, nor to a corticosteroid feedback effect.

Adrenal Cortex↗
PubMed1978

An "on-line" colorimetric method for repeated, rapid determinations of capillary diffusion capacity.

The single injection indicator diffusion method for estimation of capillary diffusion capacity (Crone 1963) has been developed to provide directly visualized, continuous colorimetric recordings of the venous time-concentration curves by means of a two-colour densitometer system. Cardio-Green, bound to albumin, is used as the non-permeant ("reference") tracer and Cr-EDTA as the permeant one. The artificially perfused hindquarter muscle vascular bed of rats is used. Highly reproducible curve recordings can be obtained every fourth minute. Accidental disturbances of the recordings are readily detected. Thus, compared to the fractional venous sampling technique, the present technique has the great advantage of allowing immediately controlled and frequently repeated determinations of capillary diffusion capacity. It is therefore easily used together with measurements of filtration-absorption events, e.g. for frequent quantitative comparisons of capillary diffusion and filtration capacities over a wide range of induced changes in perfused capillary surface area and/or capillary permeability. The main limitation is that the employed permeant tracer necessitates the use of erythrocyte-free perfusates.

Animals↗
PubMed1978

Simultaneous measurements of capillary diffusion and filtration exchange during shifts in filtration-absorption and at graded alterations in the capillary permeability surface area products (PS).

The diffusion exchange of Cr-EDTA, using the single injection indicator diffusion method, was followed simultaneously with estimations of the capillary filtration capacity (CFC) in an "isogravimetric" rat hindquarter preparation during artificial perfusion and maximal dilatation. Measurements were performed at constant flow and during 1) shifts in filtration-absorbtion, 2) alterations of perfused capillary wall area (graded rarification of capillary network by microsphere injection) and 3) during alterations of permeability (i.a. infusion of histamine). At maximal vasodilatation CFC was 0.037 +/- 0.001 ml/min X mmHg X 100 g and PS for Cr-EDTA 5.67 +/- 0.13 ml/min X 100 g. During filtration or absorbtion, Cr-EDTA transfer from vessels to interstitium changed only slightly but the situation may well be different for solute transfer from interstitium to vessels. Alterations in capillary wall area resulted in proportional changes in PS for Cr-EDTA while the CFC changes were always relatively smaller. Histamine increased CFC some threefold with a marked increase in protein transfer, while PS for Cr-EDTA increased only marginally. This histamine effect could be ascribed mainly to an increase in the number of large pores which, because of their relative paucity, are of little importance for small molecular diffusion exchange but highly important for convective and macromolecular exchange.

Absorption↗
PubMed1978

Calcium-dependent repolarization in Paramecium.

1. Intracellular injection, recording and current-passing methods were used to investigate the role of intracellular Ca in the modulation of electrical behaviour in the ciliate Paramecium caudatum.2. Injection of EGTA converted graded regenerative responses ascribed to Ca inward current to all-or-none action potentials. The EGTA injection also caused a discontinuity in the steady state I-V relations to outward current, but had little effect on hyperpolarizing current-voltage responses.3. The overshoot of the all-or-none spike produced by the EGTA-injected cell followed an approximate 29 mV increase for a tenfold increase in external Ca concentration and was independent of changes in external K and Na concentrations.4. The EGTA-induced all-or-none action potential tended to produce plateaus that could last up to 20 sec. During the plateau the membrane slowly repolarized to a critical potential, upon which repolarization occurred precipitously.5. Injection of 10(-6)M-free Ca(2+) as a Ca-EGTA buffer hyperpolarized the membrane and decreased the potential shifts to inward current pulses. These responses are consistent with an increase in K conductance.6. During EGTA plateaus reversed beating of the cilia indicated a rise in intracellular Ca, and thus an inability of the EGTA to complex the Ca as rapidly as it entered the cilia. Reversal of the motile apparatus thus appears to be activated at lower concentrations of intracellular Ca than are required to activate the inferred Ca-dependent K system.7. In uninjected cells removal of the cilia, which results in a loss of the voltage-activated Ca channels (Dunlap, 1977), or addition of extracellular Ba both tended to linearize the steady state I-V relations.8. Injections of Cs and TEA tended to linearize the steady state I-V relations, but did not result in either a conversion to an all-or-none spike or a discontinuity in the depolarizing steady-state I-V relations.9. It is concluded that in Paramecium a Ca-activated K conductance short-circuits the inward current of the regenerative Ca response, preventing all-or-none behaviour. The occurrence of plateau spikes following EGTA injection indicates that the Ca conductance inactivates very slowly in face of a maintained depolarization. Such slow Ca-inactivation is consistent with the slow relaxation of Ca-dependent ciliary reversal that occurs during maintained depolarization.10. The possibility is discussed that injection of EGTA may also enhance the Ca conductance.

Action Potentials↗
PubMed1975

Myocardial transcapillary exchange in the hypertrophied heart of the dog.

Myocardial transcapillary exchange was investigated in control hearts and in two types of hypertrophied hearts: exercise hypertrophy and pathological hypertrophy due to tricuspid insufficiency. Using the single-injection indicator diffusion method (6, 28), myocardial extractions (E), capillary clearances (C), and permeability surface area products (PS) of urea, sucrose, and inulin were measured in intact, pump-perfused, working hearts of anesthetized dogs. Both types of cardiac hypertrophy were associated with a decreased coronary vascular resistance. Myocardial E, C, and PS values from the exercised group were not significantly different from control. Dogs with pathological hypertrophy exhibited increased central venous pressures, RVEDP's, and heart rates which were greater than control values. The E, C, and PS values from the pathologically hypertrophied hearts were significantly greater than control. These increases in myocardial transcapillary exchange can be explained either by increasing the equivalent pore radius of myocardial capillary membranes from a control value of 70 to 100 A or by assuming that pathologically hypertrophied hearts have a myocardial capillary surface area available for exchange which is twice that of control hearts.

Animals↗
PubMed1977

Sites of cholinergic vasoconstriction in trout gills.

Sites of cholinergic vasoconstriction were investigated in isolated saline-perfused holobranchs of trout (Salmo gairdneri and S. trutta). Acetylcholine (ACh) always increased overall branchial vascular resistance (BVR) and, in addition, decreased the proportion of the total inflow appearing at the outflow cannula from the efferent arch artery. Since this was observed in both constant pressure and constant flow situations, it was concluded that ACh exerted most of its effect at a site downstream from the secondary lamellae, probably at the bases of the efferent filament arteries. Prussian blue dye injections indicated that, in addition, ACh caused a marked reduction in flow to the distal halves of the filaments and that flow within the proximal secondary lamellae was restricted during ACh administration to the inner and outer marginal channels of the lamellae. The results are discussed in terms of recent findings concerning the vascular anatomy of teleost gills.

Acetylcholine↗
PubMed1978

Prolonged negative feedback suppression after estradiol administration: proposed mechanism of eugonadal secondary amenorrhea.

The finding of normal gonadotropin and estradiol levels in eugonadal women with secondary amenorrhea suggests a disordered feedback relationship of the hypothalamic-pituitary-ovarian axis. To identify possible defects in negative and positive feedback, we compared the effects of five daily injections of 17 beta-estradiol (E2) in 13 normal women and 11 eugonadal patients with absent cyclic menses. The suppression phase of negative feedback was normal, as LH and FSH were similarly lowered in both groups on day 3. Continued LH (P less than 0.01) and FSH (P less than 0.02) inhibition on day 10 of the protocol, 5 days after the last E2 injection, indicated a defect in the recovery phase of negative feedback in the 11 amenorrheic women. In the 4 patients studied gonadotropin suppression persisted for 3 weeks, E2 did not blunt pituitary responsiveness to GnRH in the amenorrheic women, suggesting a central nervous system site for prolonged gonadotropin inhibition. Nine normal but only 2 amenorrheic women X2 = 4.15; P less than 0.05) exhibited a positive feedback increase in LH on days 4-6. We propose that a defect in the recovery phase of negative feedback to E2 rather than absent positive feedback may be the dominant physiological abnormality which causes secondary amenorrhea by preventing early follicular phase gonadotropin increments and follicular maturation.

Adult↗
PubMed1979

High thyroid radiation dose associated with 131-I-19-iodocholesterol adrenal scanning.

We have examined two patients undergoing 131I-19-iodocholesterol adrenal scans in order to assess thyroidal radiation dose. Thyroid uptakes of 3--5% of the administered 2 mCi dose were found despite prior administration of Lugol's iodine. Analysis of serum samples over a ten day period after iodocholesterol injection indicated that less than 10% of the radioactivity was free iodide. Kinetic results showed a high value for the thyroid/plasma 131I ratio indicating thyroid retention of 131I. This was substantiated by thyroid scintigrams. The thyroid radiation dose was estimated to be 200--250 rad for the two patients. The associated carcinogenic risk is of sufficient magnitude, in our opinion, to warrant regular follow-up of all patients who have undergone 131I-19-iodocholesterol adrenal scanning.

19-Iodocholesterol↗
PubMed1979

The efficacy of intra-articularly administered MYC 2095, triamcinolone hexacetonide and placebo in gonarthritis. A combined double-blind clinical trial.

We report the results of a double-blind three-centre study, employing a cross-over design, set up to compare the efficacy of intra-articular injections of Myc 2095 (20 mg), triamcinolone hexacetonide (Lederspan) (20 mg) and placebo in 40 patients with synovitis of the knee joint. Each patient included in the study contributed data on 2 of the 3 treatment variables being compared. Seven clinical parameters were assessed every 6 weeks, while the doctor's and the patient's assessments were scored. Intra articular treatment both with Myc 2095 and triamcinolone hexacetonide proved to be effective. Placebo response was also very high. After the first Myc 2095 injection, improvement in "tenderness", "pain under load" and "swelling and hydrops" was significantly superior to that following placebo treatment. The evaluation of the second injections indicated a marked carry-over effect from the first course. This was also evident from the doctor's and patient's assessments. The importance of including a placebo in the evaluation of anti-phlogistic drugs in clinical trials, emerged from this study.

Adult↗
PubMed1975

In vivo pulmonary metabolism of bradykinin, angiotensin I and 5-hydroxtryptamine in the rat.

Involvement of the pulmonary vasculature of the rat in the in vivo metabolism of bradykinin, angiotensin I and 5-hydroxytryptamine was studied by monitoring the systemic blood pressure response of the test animal during intravenous or intraarterial administration of these substances. Observation of essentially the same blood pressure response regardless of the route of injection indicated that neither agiotensins I or II nor 5-hydroxytryptamine was metabolized by the pulmonary vasculature, while bradykinin was inactivated to the extent of 95+% on one passage through the lung. In the rat the major portion of bradykinin inactivation and angiotensin conversion apparently occur at different places in the vascular tree and therefore could not be carried out by the same enzyme. Differential inhibition by 2-mercaptoethanol and the bradykinin potentiating peptide, Pyr-Lys-Trp-Ala-Pro, support this postulate. One rat was found which had no pulmonary kininase but could convert angiotensin I to angiotensin II. In addition, infusion of large doses of known inhibitors of lung converting enzyme had no effect on either angiotensin I conversion or bradykinin inactivation in this system. These results support the idea that the pulmonary vasculature is not a major site for conversion of angiotensin I in the rat.

Angiotensin II↗