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Biomedical subjects

C B Martin

Publications and source records attributed to C B Martin.

At least 19 recordsLinked to original sources

Analysis of the effects of activation of the alternative pathway of complement on erythrocytes with an isolated deficiency of decay accelerating factor.

E from individuals with the Inab blood group phenotype have an isolated deficiency of decay accelerating factor (DAF, CD55). DAF is a glycosyl phosphatidylinositol anchored membrane protein that inhibits activation of both the classical and alternative pathways of complement. Deficiency of DAF from the E of paroxysmal nocturnal hemoglobinuria (PNH) is thought to contribute to their greater sensitivity to complement-mediated lysis. Unlike PNH E, however, Inab cells are not susceptible to acidified serum lysis, a process that is mediated through activation of the alternative pathway. This observation led us to hypothesize that membrane constituents other than DAF control susceptibility to acidified serum lysis. To investigate this hypothesis, Inab E were incubated in acidified serum, and hemolysis and C3 deposition (as a measure of alternative pathway activation) were quantitated. C3 deposition of Inab cells was approximately 20 times greater than normal, however, hemolysis was not observed. Inab E expressed a normal amount of membrane inhibitor of reactive lysis (MIRL, CD59), a glycosyl phosphatidylinositol anchored protein that is also deficient in PNH. When MIRL function was blocked with antibody, C3 deposition markedly increased, and 100% of the Inab cells hemolyzed in acidified serum. These studies demonstrate that susceptibility to acidified serum lysis is controlled primarily by MIRL, and that in addition to its regulatory affect on the membrane attack complex, MIRL also modulates the activity of the C3 convertase of the alternative pathway by a mechanism that remains to be determined.

Animals

Fetal heart rate variability and behavioral state: analysis by power spectrum.

OBJECTIVE: We attempted to determine the relationship between the fetal heart rate power spectrum and fetal state. STUDY DESIGN: Interbeat intervals, electrocortical activity, and fetal breathing movements were recorded from five near-term fetal lambs. Interbeat intervals were taken from epochs of low-voltage electrocortical activity with breathing, low-voltage electrocortical activity without breathing, and high-voltage electrocortical activity without breathing. Power spectral techniques were applied to determine the underlying frequencies contributing to fetal heart rate variability. Spectral analysis was also performed on fetal breathing data from three animals. RESULTS: Significant differences were found between low-voltage electrocortical activity with breathing and high-voltage electrocortical activity without breathing at 0.62 Hz and from 1.09 to 1.56 Hz. There was no clear relationship between the breathing and heart rate spectra. CONCLUSIONS: Fetal heart rate is mediated by both state and respiratory variables. The respiratory component is not strictly related to respiratory rate.

Animals

[Pathogenesis of mitral valve prolapse in patients with chronic Chagas disease: study of papillary muscle myocarditis].

PURPOSE: Studying the mitral valve in chronic Chagas' heart disease, searching a possible cause effect relationship between this condition and valve prolapse. METHODS: Seventeen hearts were surveyed from individuals exhibiting chronic chagasic cardiopathy, 11 males and 6 females, aged between 31-84 (average 54) years. The hearts came from necropsies carried out until a year before. Properly preserved samples were analyzed macro and microscopically. Fragments were excised from the mitral valve papillary muscles, anterior, lateral and posterior regions of the left ventricle, interventricular septum, free wall of right ventricle and atrium walls. RESULTS: Chronic myocarditis was found ill all the samples (mild in 6 of them, moderate in 7 and severe in 4). Also, the papillary muscles exhibited myocarditis in all of the samples, and in 15 of them the degree of severity was equal to or superior than the observed in degree other regions of the heart. CONCLUSION: The chronic chagasic cardiopathy, the papillary muscle constitute a frequent site of myocarditis. This fact must be held in mind when one discusses the pathogenesis of the prolapse of the valve.

Adult

Iron absorption in hypotransferrinemic mice.

We used a unique animal model, the hypotransferrinemic (Htx) mouse, to examine the role of transferrin (Tf) in gastrointestinal iron uptake. Despite the absence of Tf, Htx animals hyperabsorb iron. Transfusion of red blood cells sufficient to normalize the hematocrit and reticulocyte count resulted in a return of iron absorption to normal values. These studies indicate that Tf does not play an obligate role in iron absorption, either as a carrier or as a humoral signal regulating absorption. Transfer of plasma or whole blood from Htx mice or from other animal models of iron hyperabsorption to normal mice did not cause an increase in iron absorption in recipient animals. Using the plasma or blood transfer approach, we have been unable to detect a humoral regulator of gastrointestinal iron absorption.

Animals

The clinical and urodynamic effects of anterior vaginal repair and Burch colposuspension.

The clinical and urodynamic effects of anterior vaginal repair and Burch colposuspension for correction of stress urinary incontinence were assessed in a prospective study. Ninety women undergoing surgery for the first time because of genuine stress incontinence were studied. A full clinical examination including simultaneous urethrocystometry according to a standardized methodology with the patients in the supine, sitting, and standing positions was performed preoperatively, 3 months postoperatively, and again 1 to 2 years later. Clinical follow-up continued for 5 to 7 years. Neither surgical anterior vaginal repair nor Burch colposuspension affected the resting variables of the urethral sphincter mechanism. After Burch colposuspension the transmitted intraabdominal pressure to the urethra significantly increased in all recording positions in all women who were successfully treated. After successful anterior colporrhaphy, the increase in pressure transmission from the abdomen to the urethra was less prominent and was only present in the sitting and standing positions. The postural changes in the urethral pressure profile characteristic of stress urinary incontinence were still present even after successful restoration of continence. The impact of successful surgery for stress incontinence is the enhancement of transmission of the intraabdominal pressure rise to the proximal urethra. This is achieved primarily by anatomic alterations rather than by altering urethral sphincter function. Burch colposuspension was more effective for the correction of genuine stress incontinence than was anterior vaginal repair.

Adult

Changes in fetal organ flow during intrauterine mechanical ventilation with or without oxygen.

To investigate whether the changes in circulation at birth are due to lung ventilation, changes in PaO2 or both we mechanically ventilated in utero the lungs of 10 fetal sheep (120-127 days of gestational age) five days after instrumentation under general anaesthesia. Electrocortical activity (ECoG), eye movements (EOG), electromyographic activity from diaphragm and posterior neck activity (EMG) and electrocardiogram (ECG) were recorded. Fetal catheters (artery and vein of the hindlimb, arteries of both forelimbs which in three occasions were advanced into the left ventricle, fetal trachea and amniotic cavity), and an endotracheal tube were placed. After recovery radioactive 15 mu microspheres (I125, Ce141, Sr85 and Sc46) were injected into the inferior vena cava or left ventricle during high voltage electrocortical activity before and after lung expansion with N2 and after expansion with O2 for two levels of PaO2. PaCO2 did not change. The percentage of spheres trapped in the lungs increased from 9.6% to 44% after expanding the lungs with N2 and to 90% when fetal PaO2 increased (P less than 0.001). Blood flow to different organs did not change during normoxic expansion but it decreased significantly to the brain (91 +/- 25 to 27 +/- 8 ml/min per 100g, [mean +/- SD]) placenta (160 +/- 57 to 54 +/- 33 ml/min/100g) and coronaries (239 +/- 91 to 117 +/- 60 ml/min per 100g) when PaO2 was increased. In conclusion fetal circulation responds to raised levels of PaO2 well before birth probably by a direct action of oxygen on the vessels.

Animals

Breathing activity in fetal sheep during mechanical ventilation of the lungs in utero.

Effects of mechanical ventilation of the lungs of fetal lambs in utero are described. Feasibility studies were performed acutely on four fetuses at 140-142 days gestational age. Five fetuses were prepared for chronic experiments at 122-128 days gestation. Mechanical ventilation was used to produce changes in fetal blood gases for periods of up to 24 h in acute preparations or for repeated periods of 3-9 h on consecutive days in chronic preparations. This technique permits the study of fetal lambs in utero under conditions which normally occur after birth without producing maternal changes or using anesthesia and whilst the umbilical circulation remains open. Four situations were examined using ventilation in these chronic preparations: (1) expansion of the lungs whilst maintaining fetal normoxia and normocapnia; (2) fetal normoxia and hypocapnia; (3) hyperoxia and normocapnia; (4) hyperoxia and hypocapnia. None of these situations produced continuous fetal breathing, either during ventilation or after switching off the ventilator. We conclude that they do not provide appropriate stimuli to mimic those which normally produce continuous breathing after birth.

Animals

Determinants of the onset of continuous air breathing at birth.

We used mechanical ventilation of the fetal lungs in utero on 11 fetal lambs at 140-145 days gestation to alter fetal blood gases and thus separate the influences of PaO2 and PaCO2 on extrauterine breathing after cord clamping. The fetus was delivered either into a 40 degrees C saline bath or onto a cold table. Mechanical ventilation was stopped 2 min after delivery and the time to onset of continuous air breathing was observed. Also two fetuses were ventilated in utero 5 or more days after chronic instrumentation at 127 days gestation; in these animals the time to onset of breathing (diaphragm EMG) was recorded after stopping the ventilator and occluding the cord. We conclude: (a) hypercapnia is a stimulus to breathing even in hyperoxia and at 40 degrees C; (b) hypocapnia delays the start of extrauterine breathing in hyperoxia at 40 degrees C; (c) hypoxia inhibits breathing in the absence of hypercapnia or cold; (d) cold overrides the effects of hypocapnia in normoxia or moderate hypoxia.

Animals

The effect of a low-dose infusion of ritodrine on cardiac output distribution and uteroplacental blood flow in unanaesthetized pregnant guinea pigs.

Cardiac output and its distribution were measured using the microsphere technique before and at 2 and 6 h during the infusion of ritodrine, 1.5 microgram X min-1 X kg-1 i.v., into near-term pregnant guinea pigs. Average cardiac output increased 16 and 25%, and total peripheral resistance decreased 16 and 19% after 2 and 6 h of ritodrine infusion. The carcass and gastrointestinal tract together received two-thirds of the extra cardiac output. Uteroplacental blood flow and uteroplacental vascular resistance were not significantly different from the preinfusion values after 2 h of ritodrine treatment, but were increased 35% and decreased 31%, respectively (p less than 0.05 and less than 0.01), after 6 h of infusion. The increase in uteroplacental blood flow between the 2- and 6-h measurements was positively, and the decrease in uteroplacental vascular resistance negatively correlated with the increase in cardiac output during the same period.

Animals

Effect of reducing uteroplacental blood flow on movements and on electrocortical activity of fetal sheep.

Eight chronically instrumented fetal sheep were asphyxiated for 1 h by partial occlusion of the uterine blood supply. Fetal movements, as reflected by phasic activity in the nuchal electromyogram, decreased during the period of asphyxia. Tonic activity also decreased. The proportion of time spent in high-voltage electrocortical activity increased. Following release of the occlusion movements returned rapidly to the level present during the control period. The distribution of electrocortical activity patterns during the recovery period was similar to that during the control period.

Animals

Effect of ritodrine on uteroplacental blood flow and cardiac output distribution in unanesthetized pregnant guinea pigs.

The effects of ritodrine, 15 micrograms X min-1 X kg-1 infused intravenously for 2 hours, on cardiac output distribution and uteroplacental blood flow were investigated in 10 chronically catheterized guinea pigs between 57 and 63 days of pregnancy. Ritodrine produced an average 29% increase in cardiac output, three quarters of which was distributed to the carcass and myocardium. Absolute placental blood flow decreased by 10%, and the placental fraction of cardiac output decreased by one third. Uteroplacental vascular resistance increased by 41% during ritodrine infusion. The proportional changes in placental blood flow were positively correlated and those in placental vascular resistance negatively correlated with the change in cardiac output.

Animals

Animal models to study fetal behaviour.

Animal models have played an important role in fetal physiological and behavioural research, and will continue to do so. They can provide important insights into processes and mechanisms, which can then be compared with findings from the more limited observations possible on the human fetus and neonate. Since each species has its own properties, however, one must be cautious in generalizing from findings obtained in these animal models to human fetal physiology and behaviour.

Animals

Effect of prolonged infusion of ritodrine on uteroplacental blood flow and cardiac output distribution in unanesthetized pregnant guinea pigs.

The effects of ritodrine, 15 micrograms X min-1 X kg-1 administered intravenously, on the maternal circulation and uteroplacental blood flow were investigated in eight chronically catheterized pregnant guinea pigs near term. Cardiac output and its distribution were measured by means of the radionuclide-labelled microsphere technique before, and after 2 and 6 h of infusion of ritodrine. Ritodrine produced a sustained elevation of cardiac output to 135 and 137% of the control value after 2 and 6 h, respectively. The carcass and gastrointestinal tract together accounted for the greatest portion of the extra blood flow, 77 and 84% at the times of the two flow measurements during treatment. After 2 h of ritodrine, mean placental blood flow was reduced to 85% of the control level (n.s.), uteroplacental vascular resistance was 127% of its initial value (n.s.), and the placental fraction of cardiac output had decreased from 18 to 12% (P less than 0.02). Continuation of the infusion to 6 h resulted in an increase in mean placental blood flow to 107% of the control value and return of uteroplacental vascular resistance to its initial level. The placental fraction of cardiac output increased to 14%, significantly (P less than 0.05) different from both the initial and the 2-h values. Blood flow to the skin, lungs, spleen and mammary glands decreased between the 2- and 6-h flow measurements. These observations are compatible with the hypothesis that the changes in uteroplacental blood flow during administration of ritodrine are passive, resulting from the balance between the increase in cardiac output and vasodilatation in extrauterine vascular beds.

Animals

The relationship between fetal activity and behavioral states and fetal breathing movements in normal and growth-retarded fetuses.

The incidence of fetal breathing was studied during the course of behavioral state observations on 28 low-risk fetuses between 32 and 40 weeks' gestational age and on 12 growth-retarded fetuses between 36 and 40 weeks. Real-time ultrasound scanners were used to detect fetal eye, body, and breathing movements, and the fetal heart rate was recorded continuously. The mean duration of the observation sessions was 110 minutes. The mean incidence of fetal breathing was greater during periods of fetal activity (body and eye movements present, greater heart rate variability) than during quiescence (body and eye movements absent, narrowed heart rate variability) at all gestational ages studied in both low-risk and growth-retarded fetuses. During periods when one of the state variables (body movements, eye movements, heart rate pattern) was in its active condition while the other two were quiet, or the reverse, the incidence of fetal breathing was intermediate between those found when all three state variables were in agreement. After behavioral states had developed, at 38 and 40 weeks, the mean incidence of fetal breathing in the low-risk fetuses was greater during active states than during the quiet state. There was no apparent increase in the degree of linkage between fetal breathing and other expressions of fetal activity after the emergence of behavioral states.

Eye Movements

Effect of isoproterenol on uterine blood flow and cardiac output distribution in pregnant guinea pigs.

The effects of isoproterenol, 0.05 micrograms X min-1 X kg-1 infused intravenously for 2 hours, on cardiac output distribution and uteroplacental blood flow were studied in six chronically catheterized guinea pigs between 60 and 68 days of pregnancy. Isoproterenol caused marked cardiac stimulation: Cardiac output was increased by 41%, of which 70% was distributed to the carcass and gastrointestinal tract. Absolute placental blood flow remained essentially unchanged, but the placental fraction of cardiac output decreased from 16% to 11%. Myometrial blood flow increased by 72%. Uteroplacental vascular resistance did not change significantly. In the guinea pig in late pregnancy beta-adrenergic receptors are present in the myoendometrial vessels but could not be demonstrated in the maternal vessels supplying the placenta.

Animals

The effect of maternal hyperoxia on breathing movements, body movements and rest-activity cycles of low-risk human fetuses.

The effects of maternal hyperoxia on fetal breathing and body movements, and on fetal activity state as reflected in the fetal heart rate pattern, were studied in 20 healthy gravida. Fetal breathing and trunk movements were observed by means of real-time ultrasound scanning, and the fetal heart rate was recorded continuously before, during and after 30 min of maternal oxygen inhalation by mask. Maternal transcutaneous oxygen tension (TcPO2) was measured in 9 subjects. The protocol was also carried out in ten of the gravidas with substitution of compressed air for oxygen. Maternal TcPO2 nearly doubled during oxygen breathing in the subjects in whom this was measured. There were no significant changes in the incidence of fetal breathing or trunk movements, or in the distribution of heart rate patterns, during maternal oxygen breathing. Also, no differences were observed in these variables between the oxygen and compressed-air experiments. We conclude that the normal level of fetal oxygenation does not limit fetal activity in uncomplicated pregnancies.

Female

Behavioural states in the fetuses of nulliparous women.

Behavioural state observations were carried out serially on the fetuses of 14 low risk nulliparae. They were observed serially at 2-weekly intervals between 32 weeks gestational age and delivery at term. Two real-time ultrasound B-scanners were used to visualize fetal body, eye and breathing movements. Fetal heart rate patterns were recorded simultaneously by means of a clinical fetal monitor. States appeared to be present transiently in three fetuses at 34 weeks. States were definitely present in five of 13 fetuses studied at 38 weeks and six of seven observed at 40 weeks. In comparison to the fetuses of low risk multiparae studied earlier, the fetuses in the present study showed a somewhat lower proportion of quiescence (coincidence 1F) and higher percentage of activity (coincidence 2F); however, most of these differences were not statistically significant. In the fetuses which showed states, the distribution and durations of the states at 38 and 40 weeks were not different from those found previously in the fetuses of multiparae. We conclude that the development of behavioural states is generally similar in the fetuses of low risk nulliparae and multiparae, but that states appear at a somewhat later gestational age in the fetuses of nulliparae.

Eye Movements