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Biomedical subjects

C G Brown

Publications and source records attributed to C G Brown.

At least 145 records · Page 8Linked to original sources

Metabolic energy pathways in Theileria annulata sporozoites and their significance in sporozoite-bovine lymphocyte interactions in vitro.

The existence of metabolic energy pathways has been studied in extracellular T. annulata sporozoites using chemicals known to inhibit specific energy-generating pathways, and their role during invasion of bovine peripheral blood lymphocytes (PBL) by the sporozoites determined in an in vitro system. An inverse relationship was depicted between the dose of various chemicals and the number of T. annulata sporozoites invading PBL: as the concentrations of the inhibitor drugs increased, the number of T. annulata sporozoites within the lymphocytes decreased. An ultracytochemical study demonstrated the presence of the respective pathway marker enzymes, i.e., lactic dehydrogenase (LDH) in the cytosol and within mitochondria, succinic dehydrogenase (SDH) on the mitochondrial membranes and in the contiguous matrix, and cytochrome oxidase (CO) between the inner and outer mitochondrial membranes, in infective T. annulata sporozoites fixed in situ within whole salivary glands of 3-day fed Hyalomma anatolicum anatolicum ticks.

2,4-Dinitrophenol↗

Comparative autoradiographic study of parasite-host-cell cyclical relationship in lymphoblastoid cell lines infected with Theileria annulata and Theileria parva in vitro.

Cyclical interactions between intracellular schizonts of the Ankara and Hissar strains of Theileria annulata and the Muguga strain of T. parva and the parasitised host lymphoblasts have been studied autoradiographically by following the incorporation of (3H) thymidine into parasite and host cell nuclei, and also by quantitating the number of schizont nuclei per lymphoblast, at various stages and phases of host cell cycle. The synthesis of DNA by Theileria schizonts and the parasitised host lymphoblasts was found to be asynchronous and to occur at different phases of the host cell interphase stage. While the lymphoblast nuclear DNA incorporates (3H) thymidine during the S phase, schizont nuclei were labelled during the G2 phase of the host lymphoblast interphase stage. The replication of schizont nuclei took place before the metaphase stage of host cell cycle, viz, prometaphase, so that the mean schizont nuclear number at host prometaphase and at anaphase--telophase was consistently more or less double the mean nuclear number at interphase.

Animals↗

Controlled clinical trials in emergency medicine.

In this first article of a series on controlled clinical trials in emergency medicine, an overview of the structure of such studies and the relevant issues related to study design, data generation, statistical analysis, and reporting are presented. The importance of precise patient selection, randomization and stratification, blinding, and equivalent therapeutic intervention in study design has been discussed. In addition, precise outcome and measurement criteria, assessor qualifications, deficiencies in data, appropriate sample-size selection, and reporting are also presented. Although an idealized framework for the conduct and analysis of a controlled clinical trial is provided, it should be appreciated that design and analytical compromises may at times be difficult to avoid in clinical research. Future articles in this series will discuss randomization in clinical trials, alternatives to randomization, beta error and sample-size determination, the statistical and analytical issues related to imperfections in the execution of a trial, and issues related to the reporting of clinical trials.

Clinical Trials as Topic↗

Immediate transthoracic pacing for cardiac asystole in an emergency department setting.

This study was conducted to prospectively evaluate immediate transthoracic pacing in the emergency department for cardiac arrest patients presenting with asystole. All adult patients presenting over an 11-month period to a university teaching hospital with asystole following nontraumatic cardiopulmonary arrest received immediate transthoracic cardiac pacing. In these 48 patients, electrical capture was achieved in 23% and mechanical capture in 17%. With subsequent intraventricular administration of epinephrine and sodium bicarbonate, the percentage of responders increased to 48% and 33%, respectively. This is a statistically significant improvement in both electrical and mechanical capture rates (P less than 0.001) as compared with historical controls in whom transthoracic pacemakers were employed several minutes into the resuscitation. In mechanical responders, blood pressure never exceeded 50 mm Hg and could not be sustained for over 2 minutes. Immediate transthoracic pacing was temporarily effective at restoring myocardial electrical and mechanical activity in a substantial number of asystolic patients. Although there were no survivors, the improved electrical and mechanical capture rates with early use of transthoracic pacing is encouraging. Future studies of transthoracic pacing in the prehospital setting appear warranted.

Adult↗

Placement accuracy of percutaneous transthoracic pacemakers.

Experience has shown that the frequency of electrical capture of the heart with percutaneous transthoracic pacemakers is disappointingly low. The authors sought to determine whether the accuracy of ventricular placement could help to explain this observation. Six approaches were used in each of twenty adult patients who were examined at autopsy. Three parasternal approaches used the fifth intercostal space (5ICS). One pacing wire was inserted immediately to the left of the sternum along the parasternal line (5ICS-PS), one wire was inserted 4.0 cm to the left of the midsternal line (5ICS-4), and the third wire was inserted 6.0 cm to the left of the midsternal line (5ICS-6). All parasternal needle insertions were directed medially, dorsally, and cephalad toward the second right costrochondral junction at an angle of 30 degrees to the skin. Three subxiphoid approaches were performed through the left xyphocostal notch at an angle of 30 degrees to the skin. One pacing wire was directed toward the right shoulder (SXRS), one toward the sternal notch (SXSN) and one toward the left shoulder (SXLS). Accuracy of ventricular placement was assessed at autopsy. The success rates for the three parasternal approaches were as follows: 5ICS-PS = 0.85; 5ICS-4 = 0.80; 5ICS-6 = 0.90. For the three subxiphoid approaches success rates were as follows: SXRS = 0.25; SXSN = 0.50; SXLS = 0.65. All three parasternal approaches had higher success rates than the SXRS approach (P less than 0.05). In addition, the 5ICS-PS and 5ICS-6 approaches were more successful than the SXSN approach (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Autopsy↗

Methods of randomization in controlled clinical trials.

In this second article of a series that explores design and analysis issues in controlled clinical trials in emergency medicine, we have discussed the case for randomization, reviewed the methods involved in simple randomization, highlighted some of the practical problems involved with randomization, and presented some modified randomization schemes intended to remedy these problems.

Clinical Trials as Topic↗

Methodology reporting in three acute care journals: replication and reliability.

As the sciences of emergency medicine and acute care medicine develop, it becomes imperative for researchers in these fields to accurately and completely report the methodology of their investigations. It is only through complete reporting that other investigators can critically examine, replicate, or expand on the results of an investigation. The purpose of our study was to compare the completeness of methodology reporting in three acute care journals, Annals of Emergency Medicine, Critical Care Medicine, and Journal of Trauma. Thirty-eight criteria characteristics necessary for the replication of a clinical trial were identified and grouped into ten categories. The categories were experimental design, recruitment and exclusion of subjects, selection of study sample, subject allocation, therapeutic regimen, blindness, outcome criteria, analysis of confounders, withdrawal of subjects, and statistical analysis. All prospective, interventional, controlled trials appearing in these journals from January 1980 to June 1983 were identified. A total of 45 trials were found. Each trial was read independently by two reviewers to determine whether each of the 38 criteria was clearly reported, not clearly reported, or not applicable. Disagreements were resolved by a third reader (adjudicator). The results are reported as the mean proportion of items clearly reported +/- standard deviation: Annals of Emergency Medicine (n = 16), 0.39 +/- 0.10; Journal of Trauma (n = 18), 0.33 +/- 0.14; and Critical Care Medicine (n = 11), 0.32 +/- 0.09. A one-way analysis of variance found no statistically significant difference between journals with respect to these proportions (P = .25).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

Injuries associated with percutaneous placement of transthoracic pacemakers.

Injuries associated with the percutaneous placement of transthoracic pacemakers are poorly documented. We prospectively sought to determine any injuries associated with various placement routes. Six different approaches were used in each of 20 adult patients examined at autopsy. Three parasternal approaches utilized the fifth intercostal space (5ICS). One pacing wire was inserted immediately to the left of the sternum along the parasternal line (5ICS-PS), one pacing wire was inserted 4 cm to the left of the midsternal line (5ICS-4), and the third wire was inserted 6 cm from the midsternal line (5ICS-6). All parasternal needle insertions were directed medially, dorsally, and cephalad toward the right second costochondral junction at an angle of 30 degrees to the skin. Three subxiphoid approaches were inserted through the left xyphocostal notch at an angle of 30 degrees to the skin. One pacing wire was directed toward the right shoulder, one toward the sternal notch, and one toward the left shoulder (SXLS). Injuries were assessed by autopsy, postmortem coronary angiography, and stereoscopic radiography. The 5ICS-PS approach resulted in fewer injuries when compared to all other approaches. Because previous work has demonstrated that the 5ICS-PS, 5ICS-6, and SXLS approaches are more accurate than the other approaches for transthoracic pacemaker insertion, the 5ICS-PS represents an approach that combines reasonable accuracy with the least likelihood for injury in the placement of percutaneous transthoracic pacing wires.

Adult↗

Reporting methodology protocols in three acute care journals.

Our study compared the reporting of methodology protocol details in three acute care journals, Annals of Emergency Medicine, Critical Care Medicine, and Journal of Trauma. Eleven criteria previously reported for evaluation of clinical trials in the medical literature were used. These were eligibility criteria, admission before allocation, random allocation, method of randomization, patients' blindness to treatment, blind assessment of outcome, treatment complications, loss to follow-up, statistical methods, statistical analysis, and power. All prospective, interventional, controlled trials appearing in the journals from January 1980 to June 1983 were identified. A total of 45 trials was found. Each study was read independently by two reviewers to determine whether each of the 11 criteria was reported clearly, reported unclearly, or not applicable. Disagreements were resolved by a third reader (adjudicator). The results are reported as the mean proportion of items clearly reported plus or minus the standard deviation: Annals of Emergency Medicine (n = 16), 0.40 +/- 0.18; Journal of Trauma (n = 18), 0.41 +/- 0.24; Critical Care Medicine (n = 11), 0.35 +/- 0.18. A one-way analysis of variance found no statistically significant difference between journals with respect to these proportions (P = .75). The study reveals that these journals, as judged by these criteria, do not report enough methodologic information to allow assessment of bias-reducing techniques and statistical methodology.

Analysis of Variance↗

Intraerythrocytic schizogony of Theileria annulata.

The intraerythrocytic multiplication of two strains of Theileria annulata was studied with parasites maintained in stationary cultures and in the blood of infected cattle. In cultures established with blood from infected cattle 20-60% of single T. annulata piroplasms divided into quadruplet forms by day 6 in vitro. Transmission electron microscopic studies of T. annulata in culture showed that piroplasms possess intracytoplasmic food vacuoles and cytostomes during a pre-division trophozoite stage. The onset of intraerythrocytic multiplication was marked by the appearance of rhoptries and electron-dense plaques beneath the parasite's plasmalemmal membrane. The plaques developed into short segments of subplasmalemmal double membranes which were closely associated with the rhoptries. It was concluded that multiplication of T. annulata in erythrocytes occurred by schizogony, as nuclear division preceded cytoplasmic division and the final separation of merozoites. The four merozoites produced by intraerythrocytic schizogony had the same ultrastructural features as the T. annulata merozoites produced by intralymphocytic schizogony. Clusters of four merozoites, identical to those observed in stationary cultures, were also seen in the erythrocytes of persistently infected cattle and appeared to represent the most significant dividing forms of T. annulata in vivo.

Animals↗

The maintenance and survival of Theileria annulata in colonies of Hyalomma anatolicum anatolicum.

Procedures are described for the colonization of Hyalomma anatolicum anatolicum ticks using gerbils, rabbits and cattle as hosts. On rabbits H. a. anatolicum undergoes a two-host cycle but methods are described for obtaining either unfed or engorged nymphs. Data are given on the life cycle timings and the numbers and timings of tick feeding regimes. The infection of H. a. anatolicum with two strains of Theileria annulata is described and methods given for monitoring the development and survival of T. annulata in H. a. anatolicum. Data are presented indicating the optimum maintenance conditions for T. annulata in H. a. anatolicum. Piroplasm parasitaemias in cattle greater than 2% gave high infection rates in adult ticks if engorged nymphs were moulted at 28 degrees C for 28 days. The Theileria will survive for ten months in such adults stored at 12 degrees C after moult, and when fed the ticks will produce maximum numbers of sporozoites on the third day of feeding, whatever their age. The moult of engorged nymphs is retarded at 18 degrees C but the Theileria in such ticks will develop normally when the ticks are moulted at 28 degrees C after four months storage at 18 degrees C.

Animals↗

Inhibition of lymphocyte invasion by sporozoites and the transformation of trophozoite infected lymphocytes in vitro by serum from Theileria annulata immune cattle.

Serum from calves immune to Theileria annulata inhibited sporozoite-induced infection and transformation of peripheral blood leucocytes (PBL) into macroschizont infected lymphoblastoid cells in vitro. Invasion by sporozoites was suppressed by some sera, especially that obtained after challenge, but in many instances suppression of infection could be attributed only to retardation of development of PBL infected with intracellular trophozoites into proliferating macroschizont infected cells. Suppression occurred both in cultures of PBL from susceptible calves and in cultures of PBL from T. annulata immune calves. More uninfected than infected blast cells were found both in cultures of PBL from susceptible calves and in cultures of PBL from immune animals. Results suggested that proliferation of uninfected PBL from susceptible calves was initiated by the transformation of sporozoite infected cells, whilst proliferation of uninfected PBL from immune calves also incorporated a component which was a mitotic response of sensitised lymphocytes to sporozoites (i.e. parasite antigen). Thymidine incorporation by cultures was a measure of proliferation of both uninfected and infected blast cells. It could be used, therefore, to monitor parasite development only where proliferation of total blast cells was directly related to proliferation of infected blasts, as in cultures of PBL from susceptible calves. This study suggests that resistance of cattle to tick derived challenge with sporozoites is mediated initially by serum factors acting both on sporozoites and on the development of intracellular trophozoites to schizonts; that the proliferation of uninfected lymphocytes in naive cattle infected with tropical theileriosis is a direct response to the proliferation of Theileria infected cells and that the proliferation of uninfected lymphocytes in Theileria immune cattle is a combined response to the proliferation of Theileria infected cells and parasite antigen.

Animals↗

Further studies on prostaglandin and thromboxane production by the rat uterus during the oestrous cycle.

Prostaglandin (PG) and thromboxane (TX) synthesis by uterine homogenates was measured at 4-h intervals during the 4-day oestrous cycle of rats. Production was in the order of 6-oxo-PGF-1 alpha (which reflects PGI-2 synthesis) greater than PGF-2 alpha greater than TXB-2 (which reflects TXA-2 synthesis) greater than or equal to PGE-2. Peak production occurred at 02:00 h on the day of oestrus, after which production gradually decreased, with some fluctuation on the day of metoestrus, to reach a minimum between 22:00 and 06:00 h on the days of dioestrus and oestrus, respectively. Separation of the uterine tissues showed that, on a unit weight basis, the endometrium had a much higher PG and TX synthesizing ability than did the myometrium, although this was compensated for on a total weight basis by the much greater mass of myometrium. Endometrial PG and TX production was in the order of PGF-2 alpha greater than TXB-2 greater than or equal to 6-oxo-PGD-1 alpha identical to PGE-2, with PGF-2 alpha and TXB-2 productions showing the greatest increases between 10:00 and 02:00 h on the days of pro-oestrus and oestrus, respectively. Myometrial PG and TX production was in the order of 6-oxo-PGF-1 alpha greater than PGF-2 alpha greater than PGE-2 identical to TXB-2, with 6-oxo-PGF-1 alpha and PGF-2 alpha productions showing small increases between 10:00 and 02:00 h on the days of pro-oestrus and oestrus, respectively. Myometrial PGE-2 production decreased between these two times.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Oestrogen-2/4-hydroxylase activity in the rat brain during lactation and throughout the oestrous cycle.

Oestrogen-2/4-hydroxylase activity was measured in whole brain, thalamus, amygdala, hypothalamus and pituitary gland of lactating rats and in whole brain of rats on different days of the oestrous cycle. Enzyme activity was increased in whole brain and in each of the brain regions examined (with the exception of the amygdala) in lactating rats. This increase in enzyme activity was associated with an increase in serum prolactin levels. During the oestrous cycle, enzyme activity in whole brain was higher on metoestrus and dioestrus than on pro-oestrus and oestrus. The decrease in enzyme on pro-oestrus was associated with an increase in both serum oestradiol and prolactin levels. These results are consistent with the hypothesis that changes in oestrogen-2/4-hydroxylase activity are associated with changes in prolactin and oestradiol secretion and may play a regulatory role in reproduction.

Amygdala↗

Glucose phosphate isomerase polymorphism in Theileria annulata and T. parva.

Six stocks of Theileria annulata isolated from the Sudan and nine stocks of T. parva, isolated in Kenya and Malawi were grown in bovine lymphoblastoid cell lines. Lysates prepared from the infected cultures were examined electrophoretically on thin layer starch gels for evidence of glucose phosphate isomerase polymorphism. The six stocks of T. annulata showed major variations in their parasite enzyme patterns but no variation was detected in nine stocks of T. parva.

Animals↗