PYROGEN-PRODUCING MOLDS AND OTHER MICROBES EXISTING IN GLUCOSE-POWDER

Abstract

Up to the earlier period of the war, undesirable reactions such as fever, chills, headache, general lassitude or fluctuation of white cell count following the intravenous injection of hypertonic or isotonic glucose-solutions were not so frequently witnessed. Consequently, these clinical reactions hardly presented any problem from the practical standpoint. Towards the end of the war, many commercial products of low quality were in wide circulation, some of which were revealed to be of substandard qualifications according to bacteriological or other routine investigative tests described in existing pharmacopoeia (J.P.V.). Thus we concede the fact that the flooding of those evidently inferior products in postwar markets is without doubt a factor which made worse the undesirable conditions of the therapeutic solution of glucose.
Yet we could not ignore the fact that the officinal products which were apparently perfect and actually made to comform to the pharmacopoeial requirements occasionally yielded febrile reactions. As our animal, chemical and bacteriological examinations will show in detail in the next report, a high percentage of these apparently normal products in question contained pyrogens, it was detected, and we were convinced of the great role of “ pyrogens ” as the cause of thermal reactions in postwar Japan.
Apart from the Billroth's experiment in 1865 as to the cause of febrile reaction due to the intravenous injection of distilled water, experiments by Wechselmann(1), Hort and Penfold(2)in 1911, Seibert(3)in 1923, Bourne and Seibert(4)in 1925, Rademaker(5) in 1930 and Co Tui and Schrift(6) in 1942 have disclosed the fact that some kinds of bacteria could produce pyrogenetic substances, the chemical and biological properties of which became clear to some extent through their efforts along with the recent research of Robinson and Flusser(7) in 1944.
Co Tui and Schrift(6) have suggested the probability of pyrogenetic reaction due to mold contamination, but Wylie and Todd(8) in 1948 reported that only bacteria were capable of producing pyrogens. Until after our preliminary report(9) on pyrogen-producing molds in 1948 no scientific news was available as for pyrogens and molds. Of late it was a great joy to know about above mentioned researches by American and English scholars and especially the report on pyrogen-producing molds by Harkness, Loving and Hodges(10) in 1950.
As our through bacteriological examinations failed to detect directly any microbe in most of the pyrogenous glucose-solution sealed in ampullae, we have been left in the dark as to whether the pyrogan which was found in the solutions in ampullae has any causal dependence to microbes or not. This is the reason why we have decided to concentrate on glucose powders as the second step in our present research.
Several years ago we successfully isolated a certain pyrogenous mold at our pharmacological institute but lost it when Professor Miyake's mycological laboratory was bombed in 1944. But, the memory of this first discovery revived our hopes in the postwar period and hence, in the present attempt to detect pyrogens and their origin, our main attention was naturally turned to molds rather than bacteria.