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HYPOTHERMIA WITH CHLORAMPHENICOL
978 ovarian tissues and the eggs are fertilised within the follicles. The pronuclear stage of the eggs is shed into the oviduct by gradual dispersion of the overlying follicle cells, and there is no remaining corona radiata to furnish the germ of the trophoblast according to Gordon’s theory. 7. " The analogy of the functions of the follicle cells and the trophoblast." Gordon’s contention here is that since the follicular epithelium functions as the nutritive membrane for the ovarian ovum, why should it not have been utilised as the nutritive membrane for the uterine embryo ? By the same reasoning it would make just as much sense to argue that the mammary epithelium is derived from trophoblast. 8. " Ontogeny and phylogeny." Probably Gordon’s confusion here results from separating in his mind the entity of trophoblast from that of chorionic ectoderm. Hubrecht was confused on this point. All available evidence (and there is much more than Hubrecht had forty years ago, or than Gordon seems aware of at present) shows that the trophoblast is the outer layer of the blastocyst and chorionic vesicle. Calling the outer layer of the blastocyst and the chorionic vesicle before invasive properties appear in it " chorionic ectoderm," and after invasiveness occurs " trophoblast," is quite all right if one feels anything in the way of understanding is gained by so doing. However, this should never be promoted to the point that beginning students or other inexperienced people forget that the invasive chorionic ectoderm or trophoblast is derived from the non-invasive type, and that in most cases the two are directly continuous with each other at the placental margins, where indeed all transitional stages between the two conditions can be seen by anyone who cares to look. 9. " The histological dissimilarity of the cytotrophoblast and the chorionic epithelium in man." There is considerable difference between the cells of the various layers of the epidermis, yet this is not thought of as evidence that they have different origins. 10. " The similarity of granulosa cells and cytotrophoblast in culture." This argument of similarity of granulosa and trophoblast cells is too flimsy to warrant more than pointing out that there is much more similarity in appearance between syncytial trophoblast and syncytia formed from the uterine epithelium than there is between granulosa and trophoblast cells. 11. " The unusual placenta of the hyracoidea." Perhaps if Gordon had read Wislocki’s 1940 paper on the placenta of Hyrax he would have been less impressed by the tendency of the mesoderm to separate from the trophoblast. 12. " The transplantation of tissues and the evidence of blood-groups." Gordon believes that if the trophoblast were of foetal origin instead of maternal it should set up an immune body reaction with the mother or host tissues. To this one can ask, what difference would it make whether the foetalmaternal contact takes place at the trophoblast-decidua level or at the mesoderm-trophoblast level if the trophoblast really were maternal tissue ? We just do not know enough about these antigen-antibody reactions in the complex situations arising in placental development to use them as evidence in such a matter. In a section entitled " The Mechanism " Gordon purports to consider the observed facts of the fate of cumulus cells and ovum in tube and uterus." These " facts " seem to add up to the following : cumulus cells are observed to fall away from the egg in the tube, but the descriptions of this falling away have in his opinion been " much exaggerated." The rest of this section is both irrelevant and conjectural. In fact even the one statement of relevant fact above, is presumptive also.
The inadequacy of the evidence for Gordon’s hypothesis emphasised by the nature of the items which he has attempted to marshal in support of it, such as Heuser and Streeter’s " slipped nuclei " and my own admittedly highly theoretical suppositions regarding the evolution of the ungulate type of epitheliochorial placenta. In another section entitled " Deductions, Placental Gonado" trophin Gordon builds up what might be called a pseudorationale of treatment of reproductive dysfunctions, &c., based on his assumption of follicular origin of trophoblast and endometrial origin of placental gonadotrophin. Also he postulates infertility due to failure of egg and follicle cells to reunite. It is certainly a waste of many things is
to carry such flights of imagination into print without sound major premise. Some of the experiments suggested to test this hypothesis would be perhaps interesting and valuable, but certainly would not disprove the often observed fact of the foetal origin of the trophoblast. There is no dearth of problems for research on the biology both of the trophoblast and of the follicular epithelium. One might point out the value of one established fact, such as the foetal origin of the trophoblast, in contrast with an even a
armchair " research " such as the article just reviewed, which has wasted much of both your time and mine. H. W. MOSSMAN Department of Anatomy, University of Wisconsin.
Associate Professor of Anatomy.
TUBERCULOSIS
SIR,—I take it that Dr. Reade, in his letter last week, is suggesting segregation of the open case of tuberculosis, Does he propose to use for this purpose our already inadequate quota of beds, or does he advocate the provision of special institutions ? These unfortunate cases certainly present a most serious problem, but instead of compulsory segregation we should rather devote our efforts to earlier diagnosis and to the eradication of sanatorium waiting-lists : these measures will ultimately do away with the problem of the open
demanding
case
Chest
B. G. RIGDEN
Clinic,
Chest Physician.
Lewes, Sussex.
HYPOTHERMIA WITH CHLORAMPHENICOL
SIR,—Squadron -Leader Briggs, in your issue of Jan. 21, described a case of typhoid fever in which, on the 5th day of treatment with chloramphenicol, the temperature fell to 95°F ; the patient complained of feeling cold, and a coarse tremor of the hands and legs appeared. This observation prompts me to record my own experience of this curious phenomenon. I was called in to see a Hindu man, aged 24, who had recently arrived from India and who gave a history of severe headache and pain in the back with continuous fever for the past week. He had been inoculated with T.A.B. vaccine about a year before. The patient looked toxic ; his temperature was 103°F. He had a dicrotic pulse with a rate of 100 per min. Bloodpressure 120/70 mm. Hg. His tongue was coated. The spleen was just palpable. Rose spots were clearly discernible on his abdomen and chest. Occasional rhonchi were heard on both sides of the chest. Typhoid fever was diagnosed clinically. Blood was taken for a Widal reaction; and this proved positive against Salmonella typhi (0 1/500 and H 1/50). Treatment was commenced with chloramphenicol. An initial dose of 1 g. was followed by 0-25 g. 2-hourly. For 72 hours the temperature remained above 103°F ; it then started to fall gradually, and 80 hours after the start of treatment it was 100.5°F. The patient’s general condition improved considerably during this period, and the toxemia. was much less. Then, 90 hours after the start of treatment, the temperature suddenly dropped to 94’5°F ; the patient became very restless and complained of a chilly sensation. The patient looked anxious ; he was not sweating, and his pulse was of good volume (the rate being 80 per min.) ; blood-pressure 115/70 mm. Hg. No tremor was detected. Chloramphenicol was stopped immediately. The patient’s condition gradually improved, and within the next few hours the temperature gradually rose to 98°F, and the symptoms slowly disappeared. No more chloramphenicol was administered. From then on, the temperature remained within normal limits and the patient made an uneventful and complete recovery.
Further observations will be required to ascertain whether hypothermia of this sort is a toxic effect of the drug, and, if so, what effect it has on the general course of the disease. B. P. ARYA. Nairobi, Kenya. ,
The inadequacy of the evidence for Gordon’s hypothesis emphasised by the nature of the items which he has attempted to marshal in support of it, such as Heuser and Streeter’s " slipped nuclei " and my own admittedly highly theoretical suppositions regarding the evolution of the ungulate type of epitheliochorial placenta. In another section entitled " Deductions, Placental Gonado" trophin Gordon builds up what might be called a pseudorationale of treatment of reproductive dysfunctions, &c., based on his assumption of follicular origin of trophoblast and endometrial origin of placental gonadotrophin. Also he postulates infertility due to failure of egg and follicle cells to reunite. It is certainly a waste of many things is
to carry such flights of imagination into print without sound major premise. Some of the experiments suggested to test this hypothesis would be perhaps interesting and valuable, but certainly would not disprove the often observed fact of the foetal origin of the trophoblast. There is no dearth of problems for research on the biology both of the trophoblast and of the follicular epithelium. One might point out the value of one established fact, such as the foetal origin of the trophoblast, in contrast with an even a
armchair " research " such as the article just reviewed, which has wasted much of both your time and mine. H. W. MOSSMAN Department of Anatomy, University of Wisconsin.
Associate Professor of Anatomy.
TUBERCULOSIS
SIR,—I take it that Dr. Reade, in his letter last week, is suggesting segregation of the open case of tuberculosis, Does he propose to use for this purpose our already inadequate quota of beds, or does he advocate the provision of special institutions ? These unfortunate cases certainly present a most serious problem, but instead of compulsory segregation we should rather devote our efforts to earlier diagnosis and to the eradication of sanatorium waiting-lists : these measures will ultimately do away with the problem of the open
demanding
case
Chest
B. G. RIGDEN
Clinic,
Chest Physician.
Lewes, Sussex.
HYPOTHERMIA WITH CHLORAMPHENICOL
SIR,—Squadron -Leader Briggs, in your issue of Jan. 21, described a case of typhoid fever in which, on the 5th day of treatment with chloramphenicol, the temperature fell to 95°F ; the patient complained of feeling cold, and a coarse tremor of the hands and legs appeared. This observation prompts me to record my own experience of this curious phenomenon. I was called in to see a Hindu man, aged 24, who had recently arrived from India and who gave a history of severe headache and pain in the back with continuous fever for the past week. He had been inoculated with T.A.B. vaccine about a year before. The patient looked toxic ; his temperature was 103°F. He had a dicrotic pulse with a rate of 100 per min. Bloodpressure 120/70 mm. Hg. His tongue was coated. The spleen was just palpable. Rose spots were clearly discernible on his abdomen and chest. Occasional rhonchi were heard on both sides of the chest. Typhoid fever was diagnosed clinically. Blood was taken for a Widal reaction; and this proved positive against Salmonella typhi (0 1/500 and H 1/50). Treatment was commenced with chloramphenicol. An initial dose of 1 g. was followed by 0-25 g. 2-hourly. For 72 hours the temperature remained above 103°F ; it then started to fall gradually, and 80 hours after the start of treatment it was 100.5°F. The patient’s general condition improved considerably during this period, and the toxemia. was much less. Then, 90 hours after the start of treatment, the temperature suddenly dropped to 94’5°F ; the patient became very restless and complained of a chilly sensation. The patient looked anxious ; he was not sweating, and his pulse was of good volume (the rate being 80 per min.) ; blood-pressure 115/70 mm. Hg. No tremor was detected. Chloramphenicol was stopped immediately. The patient’s condition gradually improved, and within the next few hours the temperature gradually rose to 98°F, and the symptoms slowly disappeared. No more chloramphenicol was administered. From then on, the temperature remained within normal limits and the patient made an uneventful and complete recovery.
Further observations will be required to ascertain whether hypothermia of this sort is a toxic effect of the drug, and, if so, what effect it has on the general course of the disease. B. P. ARYA. Nairobi, Kenya. ,