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ARTICLE |

CONTROVERSIAL POINTS IN PENICILLIN THERAPY OF OCULAR DISEASES FREE

LUDWIG VON SALLMANN, M.D.
[+] Author Affiliations

This study was supported by the Knapp Memorial Foundation.

Presented as a candidate's thesis in partial fulfilment of the requirements for membership in the American Ophthalmological Society, 1947.


Arch Ophthalmol. 1948;39(6):752-804. doi:10.1001/archopht.1948.00900020762004
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OUTLINE OF STUDY 

  • Parenteral use of penicillin

    • Passage of penicillin across blood-aqueous barrier

    • Penicillin level in ocular and other body fluids after ligation of renal vessels

    • Passage of penicillin from blood into aqueous and vitreous in ocular inflammation

  • Surface applications of penicillin

    • Solutions and ointments

    • Iontophoretic introduction of penicillin

      1. Conductivity of sodium penicillin

      2. Influence of change in hydrogen ion concentration at cathode on activity of penicillin

      3. Factors acting on passage of penicillin through cornea during iontophoresis

        • Flow of electric current from cathode

        • Changes in hydrogen ion concentration of bathing fluid

        • Polarity of terminal

        • Tonicity of penicillin solution

    • Value of high drug levels in aqueous after corneal iontophoresis or similar procedures

    • Palpebral iontophoresis

  • Local injections of penicillin

    • Under conjunctiva

    • Into anterior chamber

    • Into lens

    • Into vitreous

      1. Crystalline penicillin

      2. Penicillin and antitoxin

  • General conclusions

The literature on the use of penicillin in ophthalmology has grown extensively in the last few years

REFERENCES

(a) von Sallmann, L., and Meyer, K.:  Penetration of Penicillin into the Eye , Arch. Ophth. 31:1 ( (Jan.) ) 1944;.
(b) Struble, G. C., and Bellows, J. G.:  Studies on the Distribution of Penicillin in the Eye , J. A. M. A. 125:685 ( (July 8) ) 1944;.
(c) Bellows, J. G.:  Penicillin Therapy in Ocular Infections , Am. J. Ophth. 27:1206 ( (Nov.) ) 1944;.
(d) Leopold, I. H.:  Intravitreal Penetration of Penicillin and Penicillin Therapy of Infections of the Vitreous , Arch. Ophth. 33:211 ( (March) ) 1945;.
(e) Rycroft, B. W.:  Penicillin and the Control of Deep Intraocular Infection , Brit. J. Ophth. 29:57 ( (Feb.) ) 1945;.
(c) Town, A. E., and Hunt, M. E.:  Penicillin in the Aqueous Humor , Am. J. Ophth. 29:171 ( (Feb.) ) 1946;.
(b) Mann, I.:  Intraocular Use of Penicillin , Brit. J. Ophth. 30:134 ( (March) ) 1946;.
McDermott, W., and Nelson, R. A.:  Transfer of Penicillin into the Cerebrospinal Fluid Following Parenteral Administration , Am. J. Syph., Gonor. & Ven. Dis. 29:403 ( (July) ) 1945;.
Chow, B. F., and McKee, C. M.:  Interaction Between Crystalline Penicillin and Human Plasma Proteins , Science 101:67 ( (Jan. 19) ) 1945;.
Warburg, O. H.: Ueber die katalytischen Wirkungen der lebendigen Substanz , Berlin, Julius Springer, 1928;.
Seidel, E.:  Ueber die Gewebsatmung im Auge und ihre klinische Bedeutung , Ber. d. deutsch. ophth. Gesellsch. 45:14, 1925;.
Schmelzer, H.:  Mikrochemische Reaktionen am Ziliarepithel , Ber. d. deutsch. ophth. Gesellsch. 45:259, 1925;.
Friedenwald, J. S., and Stiehler, R. D.:  Circulation of the Aqueous: VII. A Mechanism of Secretion of the Intraocular Fluid , Arch. Ophth. 20:761 ( (Nov.) ) 1938;.
Duke-Elder, W. S.; Quilliam, J. C., and Davson, H.:  Some Observations on the Present Position of Our Knowledge of the Intraocular Fluid , Brit. J. Ophth. 24:421 ( (Sept.) ) 1940;.
Emich, F.: Microchemical Laboratory Manual , New York, J. Wiley & Sons, Inc., 1932;, p. 123.
Smith, R. G.:  A Method for the Quantitative Determination of Cyanide in Small Amounts , J. Am. Chem. Soc. 51:1171 ( (April 5) ) 1929;.
Aldridge, W. N.:  A New Method for the Estimation of Micro Quantities of Cyanide and Thiocyanate , Analyst 69:262 ( (Sept.) ) 1944;.
The silver nitrate method was not applicable, since the exposure of samples of normal aqueous to the laboratory air caused the formation of characteristic crystals of silver cyanide. The picric acid method was abandoned because of its unspecificity.
Mallory, F. B.: Pathological Technique: A Practical Manual for Workers in Pathological Histology, Including Directions for the Performance of Autopsies and for Microphotography , Philadelphia, W. B. Saunders Company, 1938;, p. 185.
Seidel.7 Schmelzer.8
Friedenwald, J. S., and Buschke, W.:  Effect of Cyanide and Other Metal Binding Substances on the Pharmacological Action of Epinephrine , Am. J. Physiol. 140:367 ( (Dec.) ) 1943;.
Cutting, W. C.; Luduene, E. P.; Fiese, M.; Elliott, H. W., and Field, J., II.:  Distribution and Fate of Penicillin in the Body , J. Pharmacol. & Exper. Therap. 85:36 ( (Sept.) ) 1945;.
Liebman, S. D., and Newman, E. H.:  Distribution of Sulfanilamide and Its Derivatives Between Blood and Aqueous , Arch. Ophth. 26:472 ( (Sept.) ) 1941;.
Beyer, K. H.; Woodward, R.; Peters, L.; Verwey, W. F., and Mattis, P. A.:  Prolongation of Penicillin Retention in the Body by Means of Para- Aminohippuric Acid , Science 100:107 ( (Aug. 4) ) 1944;.
Beyer, K. H.; Flippin, H.; Verwey, W. F., and Woodward, R.:  Effect of Para-Aminohippuric Acid on Plasma Concentration of Penicillin in Man , J. A. M. A. 126:1007 ( (Dec. 16) ) 1944;.
Beyer, K. H.; Verwey, W. F.; Woodward, R.; Peters, L., and Mattis, P. A.:  Enhancement of the Plasma Concentration of Penicillin in Dogs by the Simultaneous Administration of Para-Aminohippuric Acid , Am. J. M. Sc. 209:608 ( (May) ) 1945;.
Loewe, L.; Rosenblatt, P.; Alture-Werber, E., and Kozak, M.:  The Prolonging Action of Penicillin by Para-Aminohippuric Acid , Proc. Soc. Exper. Biol. & Med. 58:298 ( (April) ) 1945;.
Rammelkamp, C. H., and Bradley, S. E.:  Excretion of Penicillin in Man , Proc. Soc. Exper. Biol. & Med. 53:30 ( (May) ) 1943;.
Bohls, S. W., and Cook, E. B. M.:  Use of Aluminum-Penicillin Mixtures in Maintenance of Blood Levels of Penicillin: II. Combination of Delayed Absorption by Use of Aluminum-Penicillin and Renal Blockage with Benzoic Acid , Texas State J. Med. 41:342 ( (Nov.) ) 1945;.
Romansky, M. J., and Rittman, G. E.:  A Method of Prolonging the Action of Penicillin , Science 100:196 ( (Sept.) ) 1944;
 Penicillin: I. Prolonged Action in Beeswax-Peanut Oil Mixture; II. Single Injection Treatment of Gonorrhea , Bull. U. S. Army M. Dept. , October 1944;, no. (81) , p. 43.
Romansky, M. J.; Murphy, R. J., and Rittman, G. E.:  Single Injection Treatment of Gonorrhea with Penicillin in Beeswax-Peanut Oil: Results in One Hundred and Seventy-Five Cases , J. A. M. A. 128:404 ( (June 9) ) 1945;.
Romansky, M. J., and Rittman, G. E.:  Penicillin Blood Levels for Twenty-Four Hours Following a Single Intramuscular Injection of Calcium Penicillin in Beeswax and Peanut Oil , New England J. Med. 233:577 ( (Nov. 15) ) 1945;.
Nichols, D. R., and Hanuz, E. A.:  Prolonged Action of Penicillin in Mixtures of Beeswax and Peanut Oil , Proc. Staff Meet., Mayo Clin. 20:403 ( (Oct.) ) 1945;.
Kirby, W. M. M.; Leifer, W.; Martin, S. P.; Rammelkamp, C. H., and Kinsman, J. M.:  Intramuscular and Subcutaneous Administration of Penicillin in Beeswax-Peanut Oil , J. A. M. A. 129:940 ( (Dec. 1) ) 1945;.
Parkins, W.; Wiley, M.; Chandy, J., and Zintel, H. A.:  Maintenance of the Blood Level of Penicillin After Intramuscular Injection , Science 101:203 ( (Feb. 23) ) 1945;.
Leonard, G. F., and Holm, A.:  A Method for Production of Staphylococcus Toxin and Toxoid , J. Immunol. 29:209 ( (Sept.) ) 1935;.
Town, A. E.; Frisbee, F. C., and Wisda, J. G.:  Penicillin Control of Ocular Infection , Am. J. Ophth. 29:341 ( (March) ) 1946;.
Leopold, I. H.; Holmes, L. F., and La Motte, W. O., Jr.:  Local Versus Systemic Penicillin Therapy of Rabbit Corneal Ulcer Produced by Gram-Negative Rod , Arch. Ophth. 32:193 ( (Sept.) ) 1944;.
Miller, C. P.; Bohnhoff, M., and Moeller, V.:  Experimental Gonococcal Infection of the Rabbit's Eye: III. Treatment with Prophylactic and Therapeutic Agents , J. Infect. Dis. 77:216 ( (Nov.-Dec.) ) 1945;.
Brown, C. A.:  Penicillin in Ophthalmology: Bacteriological, Experimental, and Clinical Evidence of Its Value, Including a Personal Series of One Hundred and Twenty-Five Clinical Cases , Brit. J. Ophth. 30:146 ( (March) ) 1946;.
Juler, F., and Johnson, G. T.:  Use of Crystalline Penicillin in Corneal and Intraocular Infections , Brit. J. Ophth. 30:204 ( (April) ) 1946;.
Robson, J. M., and Scott, G. I.:  Production and Treatment of Experimental Pneumococcal Hypopyon Ulcers in the Rabbit , Brit. J. Exper. Path. 24:50 ( (April) ) 1943;
 Local Chemotherapy in Experimental Lesions of the Eye Produced by Staphylococcus Aureus , Lancet 1:100 ( (Jan. 23) ) 1943;
 Experimental Streptococcal Lesions of the Rabbit's Eye and Their Treatment , Brit. J. Exper. Path. 25:81 ( (June) ) 1944;.
Keyes, J. E. L.:  Penicillin in Ophthalmology , J. A. M. A. 126:610 ( (Nov. 4) ) 1944;.
Minton, J.:  Penicillin in Treatment of Common External Eye Infections , Brit. M. J. 2:324 ( (Sept. 7) ) 1946;.
Merory, P. H.; McAnally, D., and Picard, C. W.:  Penicillin for External Eye Infections , Brit. M. J. 2:513 ( (Oct. 5) ) 1946;.
von Sallmann, L.; Grosso, A. E., and Marsh, M. G.:  Ophthalmic Penicillin Ointments , Arch. Ophth. 36:284 ( (Sept.) ) 1946;.
von Sallmann and Meyer.1a Bellows.1c Leopold.1d
Milner, J. G.:  Penicillin in Ophthalmology , Brit. M. J. 2:175 ( (Aug. 5) ) 1944;.
Vincent, J. G., and Vincent, H. W.:  Filter Paper Disc Modification of the Oxford Cup Penicillin Determination , Proc. Soc. Exper. Biol. & Med. 55:162 ( (March) ) 1944;.
De Beer, E. J., and Sherwood, M. B.:  The Paper-Disc Agar-Plate Method for the Assay of Antibiotic Substances , J. Bact. 50:459 ( (Oct.) ) 1945;.
von Sallmann, L.:  Penetration of Penicillin into the Eye: Further Studies , Arch. Ophth. 34:195 ( (Sept.) ) 1945;.
Hamilton-Paterson, J. L.:  The "Ionization" of Penicillin , Brit. M. J. 1:680 ( (May 4) ) 1946;.
This penicillin was provided by Dr. O. Wintersteiner, of Squibb Institute for Medical Research. Although the preparation was analytically pure, the absence of small amounts of other penicillins (X, K and F) was not guaranteed. The content of such impurities was not likely to exceed 10 per cent.
von Sallmann, L.:  The Role of Iontophoresis with Antibiotics in Ocular Therapy , New York J. Dent. 15:261 ( (Oct.) ) 1945;.
Abramson, H. A.; Moore, D. H.; Gettner, H.; Gagarin, J., and Jennings, L.:  Isolation of an Unpigmented Skin Reactive Constituent from Extracts of Ragweed Pollen by Electrophoresis , Proc. Soc. Exper. Biol. & Med. 44:311 ( (June) ) 1940;.
Cogan, D. G., and Hirsch, E. O.:  The Cornea: VII. Permeability to Weak Electrolytes , Arch. Ophth. 32:276 ( (Oct.) ) 1944;.
von Sallmann and Meyer.1 von Sallmann.37
Wright, R. E., and Stuart-Harris, C. H.:  Penetration of Penicillin into the Eye , Brit. J. Ophth. 29:428 ( (Aug.) ) 1945;.
Rantz, L. A., and Kirby, W. M. M.:  The Action of Penicillin on Staphylococcus in Vitro , J. Immunol. 48:335 ( (June) ) 1944;.
Gerber, I. E.; Shwartzman, G., and Baehr, G.:  Penetration of Penicillin into Foci of Infection , J. A. M. A. 130:761 ( (March 23) ) 1946;.
Wirtz, R.:  Die Ionentherapie in der Augenheilkunde , Klin. Monatsbl. f. Augenh. 46:543, 1908;.
Rein, H.:  Zur Elektrophysiologie der menschlichen Haut , Ztschr. f. Biol. 84:41 ( (Jan.) ) 1926;.
Clark, W. G.; Strakosch, E. A., and Nordlum, C.:  Penetration of Sulfonamides Through the Intact Skin by Iontophoresis and Other Means of Local Application , Proc. Soc. Exper. Biol. & Med. 50:43 ( (May) ) 1942;.
Struble and Bellows.1b Leopold.1d von Sallmann.37
von Sallmann, L.:  Penicillin Therapy of Infections of the Vitreous , Arch. Ophth. 33:445 ( (June) ) 1945;.
Rycroft, B. W.:  Subconjunctival Penicillin and Intraocular Infection , Brit. J. Ophth. 29:501 ( (Oct.) ) 1945;.
Hesser, F. P., and Golland, M.:  Effect of Procaine on Inhibitory Factor of Penicillin , Mil. Surgeon 98:47 ( (Jan.) ) 1946;.
Serial dilutions of procaine hydrochloride containing 4, 2, 1, 0.5, 0.25, 0.125 and 0.06 per cent of the drug were added to appropriate mixtures of cultures of Staph. aureus in dilutions of sodium penicillin. The activity of penicillin was neither increased nor reduced.
(a) Dunnington, J. H., and von Sallmann, L.:  Penicillin Therapy in Ophthalmology , Arch. Ophth. 32:353 ( (Nov.) ) 1944;.
Ingalls, R. G.:  Penetrating Wounds of the Cornea with Hypopyon Treated with Penicillin: A Case Report , Am. J. Ophth. 29:1152 ( (Sept.) ) 1946;.
Hoskins, L. C.:  Penicillin Therapy of Experimental Infections of the Lens and Vitreons with Clostridium Welchii , Arch. Ophth. 38:301 ( (Sept.) ) 1947;.
von Sallmann, L.:  Penicillin and Sulfadiazine in the Treatment of Experimental Intraocular Infections with Staphylococcus Aureus and Clostridium Welchii , Arch. Ophth. 31:54 ( (Jan.) ) 1944;.
von Sallmann, L.; Meyer, K., and Di Grandi, J.:  Experimental Study on Penicillin Treatment of Ectogenous Infection of Vitreous , Arch. Ophth. 32:179 ( (Sept.) ) 1944;.
von Sallmann.51 Dunnington and von Sallmann.55a von Sallmann and others.59
Feigenbaum, H., and Kornbluth, W.:  Intravitreal Injection of Penicillin in a Case of Incipient Abscess of the Vitreous Following Extracapsular Cataract Extraction: Perfect Cure , Ophthalmologica 110:300 ( (Nov.-Dec.) ) 1945;.
Weizenblatt, S.:  Treatment of Acute Endophthalmitis: Report of a Case , Arch. Ophth. 36:736 ( (Dec.) ) 1946;.
One sample of crystalline sodium penicillin K and the sodium salt of crystalline penicillin G were made available through the cooperation of the Antibodies Study Section of the United States Public Health Service.
Löwenstein, A., and Samuels, B.:  Ueber Glaskörperersatz: I. Experimentelle Untersuchungen , Arch. f. Ophth. 80:500, 1911;.
Eagle, H., and Musselman, A.:  Low Therapeutic Activity of Penicillin K Relative to That of Penicillins F, G, and X and Its Pharmacological Basis , Science 103:618 ( (May 17) ) 1946;.
Coghill, R. D.; Osterberg, A. E., and Hazel, G. R.:  The Relative Effectiveness of Pure Penicillins G, X, and K , Science 103:709 ( (June 14) ) 1946;.
Van Dyke, H. B.:  Pharmacological Observations on Crystalline Sodium Penicillin , Proc. Soc. Exper. Biol. & Med. 56:212 ( (June) ) 1944;.
The lyophilized culture (36321) was obtained from the New York State Department of Health, which furnished the following data: The strain was isolated from a specimen of pus from a patient with acute mastoiditis, and its virulence for rabbits was demonstrated by intravenous injection.
McIntosh, J., and Selbie, F. R.:  Combined Action of Antitoxin and Local Chemotherapy on Cl. Welchii Infection in Mice , Lancet 2:224 ( (Aug. 21) ) 1943;.
Evans, D. G.; Fuller, A. T., and Walter, J.:  New Drugs Active in the Chemotherapy of Experimental Gas Gangrene , Lancet 2:523 ( (Oct. 21) ) 1944;.
Siebenmann, C. O., and Plummer, H.:  Chemotherapy and Antitoxin Therapy of Experimental Cl. Welchii Infection in Mice , J. Pharmacol. & Exper. Therap. 83:71 ( (Jan.) ) 1945;.
Ercoli, N.; Lewis, M. N., and Moench, L. J.:  The Antibacterial Activity of Penicillin in Experimental Infections of Mice with C. Diphtheriae , J. Pharmacol. & Exper. Therap. 84:120 ( (June) ) 1945;.
Young, R. G., and Mood, G. M.:  Effect of Penicillin on Infection of Guinea Pigs with Corynebacterium Diphtheriae , J. Bact. 50:205 ( (Aug.) ) 1945;.
Long, D. A.:  Penicillin and Diphtheria, Correspondence , Brit. M. J. 1:773 ( (May 18) ) 1946;.
Sorsby, A., and Ungar, J.:  Pure Penicillin in Ophthalmology , Brit. M. J. 2:723 ( (Nov. 16) ) 1946;.
Hobby, G. L.; Burkhart, B., and Hyman, B.:  Chemotherapeutic Action of Various Forms of Penicillin on Hemolytic Streptococcal Infections in Mice , Proc. Soc. Exper. Biol. & Med. 63:296 ( (Nov.) ) 1946;.

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(a) von Sallmann, L., and Meyer, K.:  Penetration of Penicillin into the Eye , Arch. Ophth. 31:1 ( (Jan.) ) 1944;.
(b) Struble, G. C., and Bellows, J. G.:  Studies on the Distribution of Penicillin in the Eye , J. A. M. A. 125:685 ( (July 8) ) 1944;.
(c) Bellows, J. G.:  Penicillin Therapy in Ocular Infections , Am. J. Ophth. 27:1206 ( (Nov.) ) 1944;.
(d) Leopold, I. H.:  Intravitreal Penetration of Penicillin and Penicillin Therapy of Infections of the Vitreous , Arch. Ophth. 33:211 ( (March) ) 1945;.
(e) Rycroft, B. W.:  Penicillin and the Control of Deep Intraocular Infection , Brit. J. Ophth. 29:57 ( (Feb.) ) 1945;.
(c) Town, A. E., and Hunt, M. E.:  Penicillin in the Aqueous Humor , Am. J. Ophth. 29:171 ( (Feb.) ) 1946;.
(b) Mann, I.:  Intraocular Use of Penicillin , Brit. J. Ophth. 30:134 ( (March) ) 1946;.
McDermott, W., and Nelson, R. A.:  Transfer of Penicillin into the Cerebrospinal Fluid Following Parenteral Administration , Am. J. Syph., Gonor. & Ven. Dis. 29:403 ( (July) ) 1945;.
Chow, B. F., and McKee, C. M.:  Interaction Between Crystalline Penicillin and Human Plasma Proteins , Science 101:67 ( (Jan. 19) ) 1945;.
Warburg, O. H.: Ueber die katalytischen Wirkungen der lebendigen Substanz , Berlin, Julius Springer, 1928;.
Seidel, E.:  Ueber die Gewebsatmung im Auge und ihre klinische Bedeutung , Ber. d. deutsch. ophth. Gesellsch. 45:14, 1925;.
Schmelzer, H.:  Mikrochemische Reaktionen am Ziliarepithel , Ber. d. deutsch. ophth. Gesellsch. 45:259, 1925;.
Friedenwald, J. S., and Stiehler, R. D.:  Circulation of the Aqueous: VII. A Mechanism of Secretion of the Intraocular Fluid , Arch. Ophth. 20:761 ( (Nov.) ) 1938;.
Duke-Elder, W. S.; Quilliam, J. C., and Davson, H.:  Some Observations on the Present Position of Our Knowledge of the Intraocular Fluid , Brit. J. Ophth. 24:421 ( (Sept.) ) 1940;.
Emich, F.: Microchemical Laboratory Manual , New York, J. Wiley & Sons, Inc., 1932;, p. 123.
Smith, R. G.:  A Method for the Quantitative Determination of Cyanide in Small Amounts , J. Am. Chem. Soc. 51:1171 ( (April 5) ) 1929;.
Aldridge, W. N.:  A New Method for the Estimation of Micro Quantities of Cyanide and Thiocyanate , Analyst 69:262 ( (Sept.) ) 1944;.
The silver nitrate method was not applicable, since the exposure of samples of normal aqueous to the laboratory air caused the formation of characteristic crystals of silver cyanide. The picric acid method was abandoned because of its unspecificity.
Mallory, F. B.: Pathological Technique: A Practical Manual for Workers in Pathological Histology, Including Directions for the Performance of Autopsies and for Microphotography , Philadelphia, W. B. Saunders Company, 1938;, p. 185.
Seidel.7 Schmelzer.8
Friedenwald, J. S., and Buschke, W.:  Effect of Cyanide and Other Metal Binding Substances on the Pharmacological Action of Epinephrine , Am. J. Physiol. 140:367 ( (Dec.) ) 1943;.
Cutting, W. C.; Luduene, E. P.; Fiese, M.; Elliott, H. W., and Field, J., II.:  Distribution and Fate of Penicillin in the Body , J. Pharmacol. & Exper. Therap. 85:36 ( (Sept.) ) 1945;.
Liebman, S. D., and Newman, E. H.:  Distribution of Sulfanilamide and Its Derivatives Between Blood and Aqueous , Arch. Ophth. 26:472 ( (Sept.) ) 1941;.
Beyer, K. H.; Woodward, R.; Peters, L.; Verwey, W. F., and Mattis, P. A.:  Prolongation of Penicillin Retention in the Body by Means of Para- Aminohippuric Acid , Science 100:107 ( (Aug. 4) ) 1944;.
Beyer, K. H.; Flippin, H.; Verwey, W. F., and Woodward, R.:  Effect of Para-Aminohippuric Acid on Plasma Concentration of Penicillin in Man , J. A. M. A. 126:1007 ( (Dec. 16) ) 1944;.
Beyer, K. H.; Verwey, W. F.; Woodward, R.; Peters, L., and Mattis, P. A.:  Enhancement of the Plasma Concentration of Penicillin in Dogs by the Simultaneous Administration of Para-Aminohippuric Acid , Am. J. M. Sc. 209:608 ( (May) ) 1945;.
Loewe, L.; Rosenblatt, P.; Alture-Werber, E., and Kozak, M.:  The Prolonging Action of Penicillin by Para-Aminohippuric Acid , Proc. Soc. Exper. Biol. & Med. 58:298 ( (April) ) 1945;.
Rammelkamp, C. H., and Bradley, S. E.:  Excretion of Penicillin in Man , Proc. Soc. Exper. Biol. & Med. 53:30 ( (May) ) 1943;.
Bohls, S. W., and Cook, E. B. M.:  Use of Aluminum-Penicillin Mixtures in Maintenance of Blood Levels of Penicillin: II. Combination of Delayed Absorption by Use of Aluminum-Penicillin and Renal Blockage with Benzoic Acid , Texas State J. Med. 41:342 ( (Nov.) ) 1945;.
Romansky, M. J., and Rittman, G. E.:  A Method of Prolonging the Action of Penicillin , Science 100:196 ( (Sept.) ) 1944;
 Penicillin: I. Prolonged Action in Beeswax-Peanut Oil Mixture; II. Single Injection Treatment of Gonorrhea , Bull. U. S. Army M. Dept. , October 1944;, no. (81) , p. 43.
Romansky, M. J.; Murphy, R. J., and Rittman, G. E.:  Single Injection Treatment of Gonorrhea with Penicillin in Beeswax-Peanut Oil: Results in One Hundred and Seventy-Five Cases , J. A. M. A. 128:404 ( (June 9) ) 1945;.
Romansky, M. J., and Rittman, G. E.:  Penicillin Blood Levels for Twenty-Four Hours Following a Single Intramuscular Injection of Calcium Penicillin in Beeswax and Peanut Oil , New England J. Med. 233:577 ( (Nov. 15) ) 1945;.
Nichols, D. R., and Hanuz, E. A.:  Prolonged Action of Penicillin in Mixtures of Beeswax and Peanut Oil , Proc. Staff Meet., Mayo Clin. 20:403 ( (Oct.) ) 1945;.
Kirby, W. M. M.; Leifer, W.; Martin, S. P.; Rammelkamp, C. H., and Kinsman, J. M.:  Intramuscular and Subcutaneous Administration of Penicillin in Beeswax-Peanut Oil , J. A. M. A. 129:940 ( (Dec. 1) ) 1945;.
Parkins, W.; Wiley, M.; Chandy, J., and Zintel, H. A.:  Maintenance of the Blood Level of Penicillin After Intramuscular Injection , Science 101:203 ( (Feb. 23) ) 1945;.
Leonard, G. F., and Holm, A.:  A Method for Production of Staphylococcus Toxin and Toxoid , J. Immunol. 29:209 ( (Sept.) ) 1935;.
Town, A. E.; Frisbee, F. C., and Wisda, J. G.:  Penicillin Control of Ocular Infection , Am. J. Ophth. 29:341 ( (March) ) 1946;.
Leopold, I. H.; Holmes, L. F., and La Motte, W. O., Jr.:  Local Versus Systemic Penicillin Therapy of Rabbit Corneal Ulcer Produced by Gram-Negative Rod , Arch. Ophth. 32:193 ( (Sept.) ) 1944;.
Miller, C. P.; Bohnhoff, M., and Moeller, V.:  Experimental Gonococcal Infection of the Rabbit's Eye: III. Treatment with Prophylactic and Therapeutic Agents , J. Infect. Dis. 77:216 ( (Nov.-Dec.) ) 1945;.
Brown, C. A.:  Penicillin in Ophthalmology: Bacteriological, Experimental, and Clinical Evidence of Its Value, Including a Personal Series of One Hundred and Twenty-Five Clinical Cases , Brit. J. Ophth. 30:146 ( (March) ) 1946;.
Juler, F., and Johnson, G. T.:  Use of Crystalline Penicillin in Corneal and Intraocular Infections , Brit. J. Ophth. 30:204 ( (April) ) 1946;.
Robson, J. M., and Scott, G. I.:  Production and Treatment of Experimental Pneumococcal Hypopyon Ulcers in the Rabbit , Brit. J. Exper. Path. 24:50 ( (April) ) 1943;
 Local Chemotherapy in Experimental Lesions of the Eye Produced by Staphylococcus Aureus , Lancet 1:100 ( (Jan. 23) ) 1943;
 Experimental Streptococcal Lesions of the Rabbit's Eye and Their Treatment , Brit. J. Exper. Path. 25:81 ( (June) ) 1944;.
Keyes, J. E. L.:  Penicillin in Ophthalmology , J. A. M. A. 126:610 ( (Nov. 4) ) 1944;.
Minton, J.:  Penicillin in Treatment of Common External Eye Infections , Brit. M. J. 2:324 ( (Sept. 7) ) 1946;.
Merory, P. H.; McAnally, D., and Picard, C. W.:  Penicillin for External Eye Infections , Brit. M. J. 2:513 ( (Oct. 5) ) 1946;.
von Sallmann, L.; Grosso, A. E., and Marsh, M. G.:  Ophthalmic Penicillin Ointments , Arch. Ophth. 36:284 ( (Sept.) ) 1946;.
von Sallmann and Meyer.1a Bellows.1c Leopold.1d
Milner, J. G.:  Penicillin in Ophthalmology , Brit. M. J. 2:175 ( (Aug. 5) ) 1944;.
Vincent, J. G., and Vincent, H. W.:  Filter Paper Disc Modification of the Oxford Cup Penicillin Determination , Proc. Soc. Exper. Biol. & Med. 55:162 ( (March) ) 1944;.
De Beer, E. J., and Sherwood, M. B.:  The Paper-Disc Agar-Plate Method for the Assay of Antibiotic Substances , J. Bact. 50:459 ( (Oct.) ) 1945;.
von Sallmann, L.:  Penetration of Penicillin into the Eye: Further Studies , Arch. Ophth. 34:195 ( (Sept.) ) 1945;.
Hamilton-Paterson, J. L.:  The "Ionization" of Penicillin , Brit. M. J. 1:680 ( (May 4) ) 1946;.
This penicillin was provided by Dr. O. Wintersteiner, of Squibb Institute for Medical Research. Although the preparation was analytically pure, the absence of small amounts of other penicillins (X, K and F) was not guaranteed. The content of such impurities was not likely to exceed 10 per cent.
von Sallmann, L.:  The Role of Iontophoresis with Antibiotics in Ocular Therapy , New York J. Dent. 15:261 ( (Oct.) ) 1945;.
Abramson, H. A.; Moore, D. H.; Gettner, H.; Gagarin, J., and Jennings, L.:  Isolation of an Unpigmented Skin Reactive Constituent from Extracts of Ragweed Pollen by Electrophoresis , Proc. Soc. Exper. Biol. & Med. 44:311 ( (June) ) 1940;.
Cogan, D. G., and Hirsch, E. O.:  The Cornea: VII. Permeability to Weak Electrolytes , Arch. Ophth. 32:276 ( (Oct.) ) 1944;.
von Sallmann and Meyer.1 von Sallmann.37
Wright, R. E., and Stuart-Harris, C. H.:  Penetration of Penicillin into the Eye , Brit. J. Ophth. 29:428 ( (Aug.) ) 1945;.
Rantz, L. A., and Kirby, W. M. M.:  The Action of Penicillin on Staphylococcus in Vitro , J. Immunol. 48:335 ( (June) ) 1944;.
Gerber, I. E.; Shwartzman, G., and Baehr, G.:  Penetration of Penicillin into Foci of Infection , J. A. M. A. 130:761 ( (March 23) ) 1946;.
Wirtz, R.:  Die Ionentherapie in der Augenheilkunde , Klin. Monatsbl. f. Augenh. 46:543, 1908;.
Rein, H.:  Zur Elektrophysiologie der menschlichen Haut , Ztschr. f. Biol. 84:41 ( (Jan.) ) 1926;.
Clark, W. G.; Strakosch, E. A., and Nordlum, C.:  Penetration of Sulfonamides Through the Intact Skin by Iontophoresis and Other Means of Local Application , Proc. Soc. Exper. Biol. & Med. 50:43 ( (May) ) 1942;.
Struble and Bellows.1b Leopold.1d von Sallmann.37
von Sallmann, L.:  Penicillin Therapy of Infections of the Vitreous , Arch. Ophth. 33:445 ( (June) ) 1945;.
Rycroft, B. W.:  Subconjunctival Penicillin and Intraocular Infection , Brit. J. Ophth. 29:501 ( (Oct.) ) 1945;.
Hesser, F. P., and Golland, M.:  Effect of Procaine on Inhibitory Factor of Penicillin , Mil. Surgeon 98:47 ( (Jan.) ) 1946;.
Serial dilutions of procaine hydrochloride containing 4, 2, 1, 0.5, 0.25, 0.125 and 0.06 per cent of the drug were added to appropriate mixtures of cultures of Staph. aureus in dilutions of sodium penicillin. The activity of penicillin was neither increased nor reduced.
(a) Dunnington, J. H., and von Sallmann, L.:  Penicillin Therapy in Ophthalmology , Arch. Ophth. 32:353 ( (Nov.) ) 1944;.
Ingalls, R. G.:  Penetrating Wounds of the Cornea with Hypopyon Treated with Penicillin: A Case Report , Am. J. Ophth. 29:1152 ( (Sept.) ) 1946;.
Hoskins, L. C.:  Penicillin Therapy of Experimental Infections of the Lens and Vitreons with Clostridium Welchii , Arch. Ophth. 38:301 ( (Sept.) ) 1947;.
von Sallmann, L.:  Penicillin and Sulfadiazine in the Treatment of Experimental Intraocular Infections with Staphylococcus Aureus and Clostridium Welchii , Arch. Ophth. 31:54 ( (Jan.) ) 1944;.
von Sallmann, L.; Meyer, K., and Di Grandi, J.:  Experimental Study on Penicillin Treatment of Ectogenous Infection of Vitreous , Arch. Ophth. 32:179 ( (Sept.) ) 1944;.
von Sallmann.51 Dunnington and von Sallmann.55a von Sallmann and others.59
Feigenbaum, H., and Kornbluth, W.:  Intravitreal Injection of Penicillin in a Case of Incipient Abscess of the Vitreous Following Extracapsular Cataract Extraction: Perfect Cure , Ophthalmologica 110:300 ( (Nov.-Dec.) ) 1945;.
Weizenblatt, S.:  Treatment of Acute Endophthalmitis: Report of a Case , Arch. Ophth. 36:736 ( (Dec.) ) 1946;.
One sample of crystalline sodium penicillin K and the sodium salt of crystalline penicillin G were made available through the cooperation of the Antibodies Study Section of the United States Public Health Service.
Löwenstein, A., and Samuels, B.:  Ueber Glaskörperersatz: I. Experimentelle Untersuchungen , Arch. f. Ophth. 80:500, 1911;.
Eagle, H., and Musselman, A.:  Low Therapeutic Activity of Penicillin K Relative to That of Penicillins F, G, and X and Its Pharmacological Basis , Science 103:618 ( (May 17) ) 1946;.
Coghill, R. D.; Osterberg, A. E., and Hazel, G. R.:  The Relative Effectiveness of Pure Penicillins G, X, and K , Science 103:709 ( (June 14) ) 1946;.
Van Dyke, H. B.:  Pharmacological Observations on Crystalline Sodium Penicillin , Proc. Soc. Exper. Biol. & Med. 56:212 ( (June) ) 1944;.
The lyophilized culture (36321) was obtained from the New York State Department of Health, which furnished the following data: The strain was isolated from a specimen of pus from a patient with acute mastoiditis, and its virulence for rabbits was demonstrated by intravenous injection.
McIntosh, J., and Selbie, F. R.:  Combined Action of Antitoxin and Local Chemotherapy on Cl. Welchii Infection in Mice , Lancet 2:224 ( (Aug. 21) ) 1943;.
Evans, D. G.; Fuller, A. T., and Walter, J.:  New Drugs Active in the Chemotherapy of Experimental Gas Gangrene , Lancet 2:523 ( (Oct. 21) ) 1944;.
Siebenmann, C. O., and Plummer, H.:  Chemotherapy and Antitoxin Therapy of Experimental Cl. Welchii Infection in Mice , J. Pharmacol. & Exper. Therap. 83:71 ( (Jan.) ) 1945;.
Ercoli, N.; Lewis, M. N., and Moench, L. J.:  The Antibacterial Activity of Penicillin in Experimental Infections of Mice with C. Diphtheriae , J. Pharmacol. & Exper. Therap. 84:120 ( (June) ) 1945;.
Young, R. G., and Mood, G. M.:  Effect of Penicillin on Infection of Guinea Pigs with Corynebacterium Diphtheriae , J. Bact. 50:205 ( (Aug.) ) 1945;.
Long, D. A.:  Penicillin and Diphtheria, Correspondence , Brit. M. J. 1:773 ( (May 18) ) 1946;.
Sorsby, A., and Ungar, J.:  Pure Penicillin in Ophthalmology , Brit. M. J. 2:723 ( (Nov. 16) ) 1946;.
Hobby, G. L.; Burkhart, B., and Hyman, B.:  Chemotherapeutic Action of Various Forms of Penicillin on Hemolytic Streptococcal Infections in Mice , Proc. Soc. Exper. Biol. & Med. 63:296 ( (Nov.) ) 1946;.

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