Biomedical subjects
C G Brown
Publications and source records attributed to C G Brown.
Hemorrhage from gastric mucosal tears complicating cardiopulmonary resuscitation.
We observed at autopsy two patients in whom clinically significant gastrointestinal bleeding occurred from gastric mucosal tears following closed chest cardiac massage. Review of autopsy files showed that, when the Mallory-Weiss syndrome is excluded, linear mucosal tears along the lesser curvature of the stomach occur in about 2% of patients given cardiopulmonary resuscitation; similar lesions have not been observed in patients not subjected to resuscitation. The localization of the tears along the lesser curvature of the stomach is probably the consequence of the catenoidal configuration of that region. The importance of the mucosal tears lies in their propensity to hemorrhage if resuscitation is successful.
CPR instruction: modular versus lecture course.
A randomized prospective study was done to examine long-term cardiopulmonary resuscitation (CPR) cognitive and motor skills retention and to compare the "self-taught" modular course with the standard lecture course. Both cognitive and motor skills were tested at one-, two- and four-year intervals after the initial course. Approximately half the students in both the modular and standard lecture courses also took a refresher course after one year. While there was no significant difference (P greater than .05) in retention based on the method of teaching (modular vs lecture course), students who took the refresher course after one year performed significantly better (P less than .01) at the two-year interval. Results four years after the initial CPR course (three years after the refresher course) were uniformly poor in both groups. Only three of 104 students were able to meet American Heart Association standards for the performance of CPR. Refresher courses are vital if CPR is to be performed effectively and competently. They should be available on a continuing basis with self-taught courses providing a good alternative to the formal didactic course as a means of providing instruction.
Curriculum for undergraduate education in emergency medicine.
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A histocompatibility barrier to immunization against East Coast fever using Theileria parva-infected lymphoblastoid cell lines.
Histocompatibility may be a barrier to the infection of cattle when Theileria parva parva-infected tissues or in vitro cultured macroschizont-infected lymphoblastoid cell lines are used for immunization. By inoculating 10(3) and 10(5) infected cells into autologous recipients infection was achieved and immunity engendered. Cell lines inoculated into BoLA matched recipients did not produce patent infections but some recipients developed antibodies to the parasite and 3/5 were immune to challenge. No evidence of infection or immunity was found in BoLA half matched or mismatched cattle. This result suggests that there is an histocompatibility barrier to infection using T. p. parva-infected lymphoblastoid cells.
Studies on ovarian prostaglandin production in relation to ovulation in the rat.
Prostaglandin (PG) and thromboxane (TX) synthesizing capacities of the rat ovary were measured at 4-h intervals during the 4-day oestrous cycle of the rat. Production of PGE-2, PGF-2 alpha, 6-oxo-PGF-1 alpha and TXB-2 increased 5-fold, 1.6-fold, 1.7-fold and 1.7-fold, respectively, between 18:00 h on the day of pro-oestrus and 02:00 h at oestrus. This preferential stimulation of ovarian PGE-2 production, after the ovulatory surge of LH before ovulation, provides further evidence for the involvement of ovarian PGE-2 in ovulation in the rat. These increases in ovarian PG production were not due to differences in arachidonic acid availability, PG metabolism, or the interconversion of PGE-2 and PGF-2 alpha. In addition, the greater stimulation of PGE-2 synthesis was not due to an increase in PGH-2 to PGE-2 synthetase activity. It is concluded that the ovulatory LH surge late in the afternoon of pro-oestrus in the rat causes an increase in ovarian cyclo-oxygenase (PGH-2 synthetase) activity with the majority of the PGH-2 synthesized being directed into the PGE-2-forming pathway.
Studies on the control of prostaglandin production by the hypothalamus in relation to LH release in the rat.
Prostaglandin (PG) and thromboxane (TX) synthesis by homogenates of the hypothalamus of rats has been measured in relation to the preovulatory surge of LH. Prostaglandin and TX production by the median eminence (ME) was five to ten times higher than that by the anterior hypothalamus/preoptic area (AH-POA). Prostaglandin E2 and PGF2 alpha were the major prostaglandins synthesized by the ME and AH-POA respectively. During the 4-day oestrous cycle, the PG- and TX-synthesizing capacity of the ME showed daily changes, being high at 06.00 and 22.00 h and, with the exception of pro-oestrus, low at 18.00 h. There was an additional peak of PGE2 production by the ME at 18.00 h on pro-oestrus coincident with the preovulatory LH surge. Progesterone treatment stimulated PGE2 synthesis by the ME of long-term ovariectomized, oestradiol-primed rats but not by the ME of acutely ovariectomized, oestradiol-primed rats. 2-Hydroxyoestradiol had no effect on PG and TX production by the ME at 18.00 h on dioestrus or 18.00 h on pro-oestrus. Noradrenaline stimulated PG and TX synthesis by the ME at the former time but not at the latter time. Prostaglandin F2 alpha-synthesizing capacity of the AH-POA peaked at 22.00 h on each day of the 4-day cycle. There was also an additional peak at 14.00 h on each day except dioestrus. Similar peaks occurred in the production of PGE2 and TXB2, except on pro-oestrus when the production of each compound remained low. There was no association between increased PGE2 production by the AH-POA and the preovulatory surge of LH. Noradrenaline, but not 2-hydroxyoestradiol, stimulated PG and TX production by the AH-POA at 18.00 h on both dioestrus and pro-oestrus. Progesterone stimulated PGE2, PGF2 alpha and 6-oxo-PGF1 alpha production by the AH-POA of acute, ovariectomized, oestradiol-primed rats but not of long-term ovariectomized, oestradiol-primed rats. Flurbiprofen, a cyclo-oxygenase inhibitor, prevented the preovulatory LH surge in two rats and delayed the LH surge by 2 h in four rats. It also reduced PG and TX production by the ME and AH-POA. Overall, the present studies show that there is an increase in PGE2-synthesizing capacity of the ME at the time of the preovulatory LH surge in the rat, and that the administration of an inhibitor of prostaglandin synthesis interferes with the timing of the LH surge.
Ultrastructural characteristics of in vitro parasite-lymphocyte behaviour in invasions with Theileria annulata and Theileria parva.
Host-parasite relationships have been studied by electron microscopy using glutaraldehyde-OsO4-fixed pellets of lymphoid cultures infected in vitro by Theileria annulata and T. parva. Intracellular presence of the parasite resulted in a progressive and marked lymphoblastoid transformation. The schizont stage periodically provoked the formation of, and adopted an intimate association with, cytoplasmic annulate lamellae in the interphase cell. Annulate lamellae developed from the outer nuclear membrane of the host cell by a delamination process and were taken into the cytoplasmic matrix of the schizont by phagotrophy through the cytostome. Schizont nuclei themselves were seen to divide at the prometaphase stage of host cell mitosis, the division being characterized by the development of intranuclear spindle microtubules anchored in spindle pole bodies. A hypothesis is propounded that Theileria parasites, consequent on interiorization, provoke the blastoid transformation and the formation of annulate lamellae through the influence of components of their genomic material on host cell deoxyribonucleic acid (DNA) and that the annulate lamellae represent a species of messenger ribonucleic acid (mRNA) and serve as a monitoring device for the schizont, facilitating the accurate timing of the host cell cyclical events.
Fine structure and invasive behaviour of the early developmental stages of Theileria annulata in vitro.
The interaction, in vitro, between bovine peripheral blood lymphocytes and sporozoites of Theileria annulata (Ankara) was studied by light and electron microscopy. Beginning five minutes following incubation, samples were taken for Giemsa-stained smears and glutaraldehyde-fixed pellets, for light and electron microscopy, respectively. Sporozoites of T. annulata measure an average of 0.9 microns long, 0.8 microns broad and possess a limiting unit membrane, the pellicle; a round-to-ovoid, eccentrically situated, non-chromocentric nucleus; double-membraned, tubular, acristate mitochondria; varying numbers of anisocytic, densely osmiophilic and pleomorphic organelles, the rhoptries which together with the polar ring form the apical complex; and numerous, loosely scattered, electron-dense ribosomal particles. As early as 5 min of incubation, sporozoites had made contact with, and penetrated, lymphocytes. Sporozoites consistently attached to the lymphocyte plasmalemma by their basal end, possibly at specific receptor sites. Apparently only a proportion of lymphocytes (up to 40% and more commonly 10-20%) were susceptible. Two subpopulations of the susceptible lymphocytes were observed; one which appeared to have receptor sites localized on one pole of the plasmalemma and the other subpopulation in which the receptor sites were distributed evenly around the plasmalemmal surface. Within individual susceptible lymphocytes, the number of interiorized sporozoites increased from 1 to 3 at 5-10 min to as many as 15 or more parasites at around 60 min of incubation. Theileria annulata sporozoites were interiorized by the invagination of the host cell plasmalemma which remained intact throughout the process but later fragmented. Within 30 min of interiorization, each sporozoite underwent dedifferentiation by the loss of its rhoptries and transformed into a trophozoite. Around 24 h, the trophozoite, a uninucleate, motile and feeding stage of the parasite, developed into a schizont by an acentric, closed mitosis.
Duration of residency training.
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Delirium with phenytoin and disulfiram administration.
The case of a 54-year-old man with delirium secondary to phenytoin and disulfiram administration is presented. The pharmacology, interaction, and resulting toxicity of these two drugs are explored. The patient made an uneventful recovery when the medications were withheld.
The alcohol-withdrawal syndrome.
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Cell-mediated cytotoxicity in Theileria annulata infection of cattle with evidence for BoLA restriction.
Recovery of calves from tropical theileriosis was accompanied by the disappearance of macroschizonts from lymph nodes and the appearance of cytotoxic cells in the blood and lymph nodes. Acute, fatal disease was associated with incremental parasitosis and parasitaemia and, in general, an absence of detectable cytotoxic cells in the blood or lymph nodes. After recovery from infection, calves were resistant to challenge. Challenge with sporozoites was followed sometimes by an immediate reappearance or by a later peak, or sometimes by twin peaks of cytotoxic cells but macroschizonts were not detected. Histocompatibility (BoLA) typing indicated that calves produced two sequential populations of cytotoxic cells during recovery from primary infection with Theileria annulata. The expression of lysis by the first appeared to be BoLA restricted. In contrast, both the peaks of lysis manifest after challenge appeared to be BoLA restricted. Results suggest that BoLA restricted cells are established in the immunological memory and are probably analogous to cytotoxic T cells, while non-BoLA restricted cytotoxic cells are natural killer like cells. The results suggest a role for cytotoxic cells in recovery from primary infection, in the inhibition of proliferation of macroschizonts which evade mechanisms of acquired resistance and in the lysis of macroschizont infected cells deriving from challenge sporozoites which have evaded serum-mediated inhibition.
The alcohol withdrawal syndrome.
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The fine structural relationship between Theileria schizonts and infected bovine lymphoblasts from cultures.
The fine structure of Theileria-lymphoblast relationship was studied using cultured bovine lymphoblastoid cells infected with Theileria parva, T lawrencei, or T. annulata. The major findings of this study were: (1) the presence of a very active Golgi complex with the associated annulate lamelae; (b) the presence of cytoplasmic microtubules which joined the parasites and host cell centriole during lymphoblast mitosis; and (c) the absence of morphological evidence to suggest that the host cell developed a reaction to the parasitic presence. The significance of these findings is discussed.
Identification of Theileria infections in the salivary glands of Hyalomma anatolicum anatoli cum and Rhipicephalus appendiculatus using isoenzyme electrophoresis.
Lysates prepared from the salivary glands of uninfected Hyalomma anatolicum anatolicum and Rhipicephalus appendiculatus and from ticks of these species infected with 2 strains of Theileria annulata and 1 strain of T. parva respectively have been examined for enzyme polymorphism using thin layer starch gel electrophoresis. Representative enzymes from 3 of the major metabolic pathways, the tricarboxylic acid cycle, the glycolytic pathway and the pentose phosphate pathway were investigated. Only 1 enzyme, glucose phosphate isomerase, showed differences between the host cell activity and the parasite activity and also inter- and intraspecific differences between the parasites. This technique represents a useful complement to the present histochemical methods for identification of Theileria infections in the salivary glands of ticks.
Preliminary investigations on isoenzyme variants of lymphoblastoid cell lines infected wih Theileria species.
The electrophoretic mobilities of seven enzymes from eight theileria-infected bovine lymphoblastoid cell lines originating in Kenya and Iran were compared. The isoenzyme patterns of phosphoglucomutase, malate dehydrogenase, malic enzyme and glucose-6-phosphate dehydrogenase were the same for all cell lines infected with any of the three Theileria species. Theileria annulata could be clearly differentiated from T parva and T lawrencei on the basis of three enzymes: glucose phosphate isomerase, glyceraldehyde phosphate dehydrogenase and aldolase. T parva and T lawrencei isoenzyme patterns were alike except for glucose phosphate isomerase, where two sets of isoenzyme mobility were shown which, however, did not separate the two species.