Biomedical subjects

L Carmichael

Publications and source records attributed to L Carmichael.

At least 19 recordsLinked to original sources

PubMed1992

Effects of sustained hypoxemia on the sheep fetus at midgestation: endocrine, cardiovascular, and biophysical responses.

OBJECTIVE: The purpose of our study was to examine the effects of induced hypoxia on endocrine, cardiovascular, and biophysical measurements of the ovine fetus at 0.6 (83 to 93 days) of gestation and to compare the fetal responses at this earlier gestation with those reported near term. STUDY DESIGN: Fourteen fetal sheep were studied (9 in the hypoxia group and 5 in the control group) at 0.6 of gestation during a 24-hour control period, 8 hours of either sustained hypoxemia or room air, and a 40-hour recovery period. RESULTS: Induced fetal hypoxemia resulted in a progressive lactic metabolic acidosis; however, all fetuses had recovered within 24 hours. The fetal endocrine response was variable with norepinephrine, the only measured hormone showing a significant hypoxia-related increase (p less than 0.05). Fetal heart rate and mean arterial blood pressure showed little hypoxia-induced change, although fetal heart rate was significantly increased over the first 2 hours (p less than 0.05). The percent time fetal breathing movements, electroocular activity, and nuchal muscle activity likewise showed little hypoxia-induced change. CONCLUSION: The cardiovascular and biophysical response of the preterm fetus to induced hypoxemia is thus much less pronounced than that of the older gestational-aged fetus; this difference may impact on survival and the success of antenatal assessment protocols.

Animals↗

PubMed1992

Electrocortical activity, electroocular activity, and breathing movements in fetal sheep with prolonged and graded hypoxemia.

OBJECTIVE: Our objective was to determine the effect of a prolonged and graded reduction in fetal arterial oxygen saturation on electrocortical activity and associated biophysical variables. STUDY DESIGN: Fourteen unanesthetized fetal sheep were studied between 126 and 135 days' gestation with continuous monitoring of electrocortical and electroocular activity and breathing movements, during a 24-hour control period, and subsequently during 4 days of prolonged and graded hypoxemia induced by progressively lowering the maternal inspired oxygen concentration. RESULTS: Graded reduction in fetal arterial oxygen saturation resulted in little change in arterial pH until close to 30% when metabolic acidemia was apparent. The incidence of low-voltage electrocortical activity, electroocular activity, and breathing movements were marginally decreased with hypoxemia alone; however, a significant decrease was not apparent until associated with the onset of fetal acidemia. CONCLUSION: Hypoxemia of a chronic nature must approach the level at which acidemia becomes apparent before a marked change in fetal behavioral activity is noted.

Animals↗

PubMed1992

Voices from family medicine: Lynn Carmichael. Interview by William B. Ventres and John J. Frey.

Now that the 25th anniversary of the Society of Teachers of Family Medicine is upon us, educators are likely to look back at the history, which set the stage for family medicine. This is a history replete with reports, politics, and ultimately, the development of family practice training programs. It is a history, as well, made through the labors of individuals. The vantage points we have chosen to examine in this series are those of some of the people who lent their efforts to the founding of family medicine. Common personal needs prompted us to explore these vantage points. Although we are at different points in our professional trajectories--one of us is a recent graduate from residency and fellowship training, the other has many years of experience as a teacher and journal editor--the same themes emerged in our self-explorations. Where do we fit into the family medicine movement? What satisfaction do we get out of our day-to-day routines of practice, teaching, and research? What meaning sustains our activities in the discipline? To help answer these questions, we looked to some of the leaders of family medicine. In this transcript, an abridged and edited version of interviews conducted in April and May of 1991, Lynn Carmichael, MD, discusses his involvement with the founding of family medicine, his perspectives on the importance of family practice, and his thoughts and concerns about the future. Dr. Carmichael is professor and founding chair of the Department of Family Medicine at the University of Miami School of Medicine. He was the first president of the Society of Teachers of Family Medicine, the founding editor of Family Medicine (then Family Medicine Teacher), and the initial recipient of the STFM Certificate of Excellence in 1978.

Career Choice↗

PubMed1991

The effects of indomethacin and prostaglandin E2 on the ethanol-induced suppression of ovine fetal breathing movements.

A study was performed to examine the role of prostaglandins (PGs) in the mechanism of the ethanol-induced suppression of FBM, in which the objective was to test the hypothesis that fetal administration of PGE2 can suppress the incidence of FBM following reversal of ethanol-induced suppression of FBM by indomethacin, a fatty acid cyclooxygenase inhibitor. Instrumented near-term pregnant ewes received 1-h maternal infusion of ethanol (1 g/kg maternal body weight) followed 0.5 h later by a 3-h fetal infusion of indomethacin (1 mg/kg fetal body weight/h), and then a 2-h fetal infusion of PGE2 (400 ng/kg fetal body weight/min). Prior to drug administration, FBM occurred approximately 36.1 +/- 2.6% of the time. FBM were suppressed during the period of ethanol infusion (9.6 +/- 1.7%); the ethanol-induced suppression of FBM was reversed by fetal indomethacin treatment (77.5 +/- 14.1%); shortly after the onset of fetal PGE2 infusion, the incidence of FBM decreased to a 2-h mean incidence of 14.1 +/- 4.2%, which was similar in magnitude to that observed after maternal ethanol infusion. After the completion of PGE2 infusion, the incidence of FBM rapidly increased to a peak incidence of 83.4 +/- 19.2%, which was indicative of a prolonged effect of indomethacin on FBM. The data indicate that PGs mediate the ethanol-induced suppression of ovine FBM and that the action of indomethacin to antagonize ethanol-induced suppression of FBM is primarily due to its inhibition of PG synthesis.

Animals↗

PubMed1990

Oxygen consumption in the fetal lamb during sustained hypoxemia with progressive acidemia.

To investigate the fetal ability to compensate for a sustained reduction in O2 delivery (DO2; umbilical blood flow X umbilical venous O2 content), studies were carried out on eight chronically instrumented fetal lambs made hypoxemic for 7.8 +/- 0.8 (+/- SE) h by lowering maternal inspired O2 concentration to 9-10%. After 1.7 h of hypoxemia, fetal arterial PO2 had fallen from 18.4 +/- 1.2 to 10.4 +/- 0.5 mmHg. Umbilical venous O2 content fell initially by 41.1 +/- 1.8%, but the fall in DO2 was only 23.7 +/- 5.6%, caused by a 29.3 +/- 7.9% rise in umbilical blood flow. Fetal O2 consumption (VO2) was increased significantly by 29.5 +/- 15.2%. However, fetal vascular pH (7.332-7.281) and base excess (0.5 to -4.3 meq/l) were decreased while blood lactate levels were increased (1.55-7.22 mM). With continued hypoxemia, the metabolic acidemia worsened and led to progressive declines in umbilical venous O2 content and DO2. However, VO2 was maintained at the control level until delivery had fallen by 72.5% and arterial pH was 6.843, at which time VO2 decreased by 37.5 +/- 10.7%. It is concluded that the ability of the fetus to compensate for sustained hypoxemia is limited by the progressive metabolic acidemia.

Acid-Base Equilibrium↗

PubMed1990

Blood flow and oxygen delivery to fetal organs and tissues during sustained hypoxemia.

To examine the fetal cardiovascular responses to a sustained reduction in O2 delivery (DO2), studies were conducted on 13 chronically instrumented fetal lambs (128-138 days gestation) made hypoxemic for 7.9 +/- 0.5 h by lowering maternal inspired O2 concentration to 9-10%. Fetal descending aortic PO2 fell initially from 18.0 +/- 1.0 to 10.7 +/- 0.6 mmHg, whereas pH decreased progressively from 7.326 +/- 0.006 to 6.843 +/- 0.023. Blood flow to the cerebral hemispheres, myocardium, and adrenal glands rose maximally by 110.2 +/- 22.5, 253.7 +/- 41.1, and 338.7 +/- 55.0%. Cerebral hemispheric DO2 fell progressively, whereas DO2 to the myocardium and adrenal was maintained until 7.9 h, when it fell significantly. There was also a rise in blood flow to brown adipose tissue. Blood flow to the gut and skeletal muscle was maintained, whereas flow to the spleen and kidney fell. DO2 to all these tissues fell markedly because of the progressive decline in blood O2 content. It is concluded that fetal cardiovascular function was well maintained in the face of severe hypoxemia and marked acidemia.

Animals↗

PubMed1990

Indomethacin reversal of ethanol-induced suppression of ovine fetal breathing movements and relationship to prostaglandin E2.

The effects of indomethacin on the ethanol-induced suppression of fetal breathing movements and fetal arterial plasma and cerebrospinal fluid (CSF) PGE2 concentrations and maternal arterial plasma PGE2 concentration were determined in the near-term fetal lamb. Eight conscious instrumented pregnant ewes (between 130 and 133 days of gestation; term, 147 days) received 1-h maternal intravenous infusion of 1 g ethanol/kg total body weight, and the fetus received 6-h intravenous infusion of indomethacin (1 mg/h per kg fetal body weight) commencing 30 min later. Serial fetal and maternal arterial blood samples (n = 8) and fetal CSF samples (n = 5) were collected at selected times throughout the 12-h study for the determination of PGE2 concentration. Fetal breathing movements were monitored continuously throughout the experimental period. Maternal ethanol infusion resulted in initial suppression (P less than 0.05) of fetal breathing movements for 2 h below pretreatment value, followed by a rapid increase in the incidence of fetal breathing movements after the onset of fetal indomethacin treatment. Fetal and maternal plasma PGE2 concentrations and fetal CSF PGE2 concentration were increased (P less than 0.05) above the pre-infusion value during the administration of ethanol and 1 h thereafter. Fetal indomethacin treatment suppressed (P less than 0.05) to undetectable levels fetal plasma and CSF PGE2 concentrations, which then became similar (P greater than 0.05) to pretreatment by 12 h. There was a positive correlation between fetal plasma and CSF PGE2 concentrations. There was an inverse correlation between the incidence of fetal breathing movements and fetal CSF PGE2 concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Effect of ethanol on ovine fetal and maternal plasma prostaglandin E2 concentrations and fetal breathing movements.

The effect of maternal administration of ethanol on fetal and maternal plasma prostaglandin E2 (PGE2) concentrations and fetal breathing movement was determined in the near-term pregnant ewe. Six conscious instrumented pregnant ewes (between 129 and 134 days of gestation; term, 147 days) were studied on two successive days (day 1 and day 2). On each of the two days of the experiment, there was a 1-h period of maternal infusion of ethanol (1 g ethanol/kg total body weight) or an equivalent volume of normal saline. Animals were assigned to two groups with one group (n = 3) receiving ethanol on day 1 and saline on day 2, and the other group (n = 3) receiving saline on day 1 and ethanol on day 2. Fetal and maternal blood samples were collected at selected times for blood ethanol determination (n = 2), and plasma was obtained for the determination of PGE2 concentration (n = 6). Fetal breathing movements were monitored continuously during the experimental periods. Maternal saline infusion had no effect (P greater than 0.05) on fetal breathing movement and fetal and maternal plasma PGE2 concentrations (187 +/- 25 (SEM) pg/ml and 196 +/- 32 pg/ml, respectively). Maternal ethanol infusion suppressed (P less than 0.05) fetal breathing movement below preinfusion levels for 8 h and increased (P less than 0.05) both fetal and maternal plasma PGE2 concentrations to 314 +/- 55 pg/ml and 306 +/- 25 pg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

PubMed1989

Vibratory acoustic stimulation in 26- to 32-week, small-for-gestational-age fetus.

Seven pregnant women with early-onset (less than 32 weeks' gestation) intrauterine growth retardation were studied to examine fetal heart rate and fetal activity patterns after vibratory acoustic stimulation. All studies were done between 26 and 32 weeks' gestation. All fetuses but one were not acidotic at birth. There was a reduced time during which accelerations (50% less), long-term fetal heart rate variability (25% less), and body movements (60% less) occurred in small-for-gestational-age fetuses compared with these times in age-matched normally grown fetuses. Fetal heart rate and fetal activity patterns were not significantly altered after stimulation with the electronic artificial larynx. We hypothesized that severe, early-onset (less than 32 weeks' gestation), chronic nutritional deprivation of human fetuses is associated with a delay in the functional maturation of fetal sensory receptors.

Acoustic Stimulation↗

PubMed1989

Regional blood flow change in the lamb during the perinatal period.

Regional blood flow distribution was studied with a radioactive-labeled microsphere technique in 11 unanesthetized fetal sheep (139 to 143 days' gestation). After cesarean delivery each neonatal lamb was studied at 2 and 24 hours of age. Blood flow to the cerebral hemispheres and adrenal glands decreased progressively after birth and correlated inversely with the postnatal rise in arterial oxygen content (r = -0.77, p less than 0.001 and r = -0.52, p less than 0.01, respectively). Blood flow to the gastrointestinal tract and kidneys changed little despite the known increase in blood flow from the late fetal to the early neonatal period. Skeletal muscle and brown fat blood flow were both increased when measured at 2 hours after birth, with an even greater increase in their respective oxygen deliveries presumably reflecting their increased metabolic activity with thermogenesis at this time. Variable blood flow changes are thus evident over the immediate perinatal period. In some cases these changes reflect birth-related changes in either blood gases or functional activity whereas in others the changes simply reflect a continuum from the late fetal to the early neonatal period.

Animals↗

PubMed1989

Control of fetal breathing in the human fetus between 24 and 34 weeks' gestation.

The effect of induced maternal hypocapnia and hypercapnia on fetal breathing movements was studied in 30 healthy pregnant women between 24 and 34 weeks' gestation to determine whether gestational age influences the fetal respiratory response to alterations in carbon dioxide levels. The percent time of fetal breathing movements correlated significantly with maternal end-tidal PCO2, increasing with maternal breathing of 2% and 4% carbon dioxide and decreasing with maternal hyperventilation for each of the three gestational age groups studied. However, the slope of this response for the 28- to 30-week group (3.29) and for the 32- to 34-week group (3.66), although similar to that of the term fetus, was significantly greater than that for the 24- to 26-week group (1.18, p less than 0.001). We conclude that the carbon dioxide level in the preterm fetus (as in the term fetus) is an important stimulus for the generation of respiratory movements. However, a developmental change is evident; the 24- to 26-week fetus demonstrates a decreased respiratory response to tonic carbon dioxide input. This may account for the decreased incidence of fetal breathing movements in the fetus of younger gestational age.

Carbon Dioxide↗

PubMed1989

Adrenocorticotropic hormone, cortisol, and progesterone changes in the lamb during the perinatal period.

Although the changes in circulating concentrations of adrenocorticotropic hormone, cortisol, and progesterone are well established for the fetal and neonatal lamb, there is little information on these hormones in the immediate perinatal period. We have examined the relationship between these hormones and systemic blood gas tensions and substrate concentrations in the perinatal period. Measurements were made in arterial blood of seven unanesthetized fetal sheep at 138 to 141 days' gestation during low- and high-voltage electrocortical activity. After cesarean delivery each newborn lamb was studied again at 2, 5, and 10 minutes and at 2 and 24 hours while awake. There was no correlation between fetal or maternal adrenocorticotropic hormone, cortisol, or progesterone and fetal electrocortical activity. Within 2 to 5 minutes of delivery there was a dramatic increase in neonatal immunoreactive adrenocorticotropic hormone concentrations associated with an increase in plasma cortisol. Neonatal Pao2 rose progressively, but a mixed respiratory and metabolic acidosis was evident during the first 10 minutes after delivery. This was partially corrected by 2 hours of neonatal life and was fully corrected by 24 hours of life. We conclude that rapid responsiveness of the fetal pituitary-adrenal axis occurs in response to birth in the absence of active labor, and we suggest that this may have survival value for the preterm fetus.

Adrenocorticotropic Hormone↗

PubMed1989

Effect of acute, multiple-dose ethanol on maternal and fetal blood gases and acid-base balance in the near-term pregnant ewe.

The effect of ethanol on maternal and fetal blood gases and acid-base balance was determined in six conscious instrumented near-term pregnant ewes for maternal intravenous infusion of 3 g ethanol/kg total body weight administered as six doses of 0.5 g ethanol/kg total body weight over 8 h. Maternal and fetal blood ethanol concentrations, determined in two animals, were maximal at 8 h (3.74 and 3.82 mg/mL, respectively) and were virtually identical during the 24-h study. Maternal and fetal blood gases and acid-base balance were not significantly altered during and after ethanol administration compared with preinfusion values. The data demonstrate that, during near-term ovine pregnancy, the equivalent of a binge-type drinking episode does not produce fetal hypoxia or acidosis. Furthermore, these data do not support the postulated involvement of ethanol-induced fetal hypoxia in the mechanism of ethanol teratogenesis.

Acid-Base Equilibrium↗

PubMed1989

Cerebral oxidative metabolism in lambs during perinatal period: relationship to electrocortical state.

Cerebral oxidative metabolism and regional blood flow were studied, with changes in behavioral state over the immediate perinatal period, to determine the change in cerebral metabolism at birth and the relationship to behavioral activity. Nine unanesthetized fetal sheep (139-142 days gestation) were each studied during a period of high-voltage and low-voltage electrocorticogram (ECOG) activity and then again after cesarean delivery at 2 h of age while awake and at 24 h of age while awake and during a period of high-voltage ECOG sleep. Preductal arterial and sagittal vein blood samples were analyzed for O2 content, blood gases, and pH. Blood flow was measured with a radioactive microsphere technique. Cerebral oxidative metabolism showed no significant perinatal change, although a coupling to behavioral state was evident with significant increases during both the perinatal low-voltage ECOG state and the awake state at 24 h. Blood flow to the brain showed a significant perinatal decrease after birth and state-related increases during both the prenatal low-voltage ECOG state and the awake state at 24 h consistent with the tight coupling of flow and/or O2 delivery to metabolic needs reported for normal brain tissue. The cerebral metabolic rate of the prenatal low-voltage ECOG state suggested a level of functional excitation comparable with that of the awake state after birth, supporting the importance of the rapid-eye-movement (REM) state mechanism as a source of endogenous stimulation during the perinatal period of brain growth and development.

Animals↗

PubMed1989

Development of tolerance to ethanol-induced suppression of breathing movements and brain activity in the near-term fetal sheep during short-term maternal administration of ethanol.

The effect of short-term maternal ethanol administration on the ethanol-induced suppression of fetal breathing movements, electrocortical (ECoG) activity, and electroocular (EOG) activity was determined in the near-term fetal sheep. Twelve conscious instrumented pregnant ewes (between 125 and 139 days of gestation; term, 147 days) received 1-h intravenous infusion of 1 g ethanol/kg total body weight daily for six days (n = 6) or an equivalent volume of normal saline daily for six days (n = 6). On the seventh day, the ethanol- and saline-pretreated animals were administered 1 g ethanol/kg total body weight. A further six ewes received 1-h intravenous infusion of 1 g ethanol/kg total body weight (n = 3) or an equivalent volume of normal saline (n = 3) daily for thirteen days with both groups receiving 1 g ethanol/kg total body weight on day fourteen. Fetal ECoG and EOG activities, and fetal breathing movements were monitored continuously over the post- operative and experimental periods. Saline infusion had no significant effect on the parameters studied. Fetal breathing movements were suppressed for 8 h after the first ethanol dose, and were not significantly suppressed after fourteen days of once-daily, maternal ethanol administration. Low-voltage ECoG and EOG activities were suppressed for 3 h after the first ethanol dose, and were not significantly suppressed after seven days of repeated ethanol administration. Maternal and fetal blood gases and acid-base balance were not significantly affected by maternal ethanol administration. These data demonstrate that short-term maternal administration of ethanol results in the development of tolerance to ethanol in the mature fetus.

Animals↗

PubMed1989

Indomethacin antagonizes the ethanol-induced suppression of breathing activity but not the suppression of brain activity in the near-term fetal sheep.

The effect of indomethacin on the ethanol-induced suppression of fetal breathing movements, low-voltage electrocortical (ECoG) activity, and electro-ocular (EOG) activity was studied in the near-term fetal sheep. Ten conscious instrumented pregnant ewes (between 129 and 131 days of gestation; term, 147 days) received 1-h maternal intravenous infusion of 1 g ethanol/kg total body weight and simultaneous fetal treatment with either indomethacin (2 mg/kg fetal body weight/h) (n = 5) or an equivalent volume of phosphate buffer (n = 5) intravenously for 9 h. Fetal ECoG activity, EOG activity, and fetal breathing movements were monitored continuously over the experimental periods. In animals treated with ethanol and buffer (n = 5), fetal breathing movements were suppressed for 8 h and low-voltage ECoG and EOG activity was suppressed for 2 h below preinfusion levels. In animals treated with ethanol and indomethacin (n = 5), fetal breathing movements were elevated for 13 h but low-voltage ECoG and EOG activity remained suppressed for 3 h below preinfusion levels. The data suggests that indomethacin can antagonize the ethanol-induced suppression of fetal breathing movements, but does not alter the ethanol-induced suppression of ECoG or EOG activity.

Animals↗

PubMed1989

Epidemiology of anencephaly in Texas, 1981-1986.

The incidence of anencephalic births among Texas residents for the period 1981 through 1986 is described. The annual incidence of this birth defect varied from 3.8 to 4.3 cases per 10,000 total births (live births and stillbirths). The highest mean annual incidence was found in East Texas and South Texas. Within all ethnic and racial groups studied, females had higher rates of anencephaly than males, and Spanish-surnamed residents had the highest incidence of this defect, with 5.0 cases per 10,000 live births. Mothers with three or more previous live births or a history of stillbirths were more likely to have anencephalic offspring than were those without these documented histories. Differences in the incidence of anencephalic births between Spanish-surnamed and non-Spanish-surnamed whites were not explained by differences in parity.

Anencephaly↗

PubMed1989

Cerebral oxidative metabolism during sustained hypoxaemia in fetal sheep.

Cerebral oxidative metabolism was determined in 9 unanaesthetized fetal sheep near term, during a normoxic control period and during sustained hypoxaemia induced by lowering maternal inspired O2 concentration to 11-8% with 3% CO2 added. Preductal arterial and sagittal vein blood samples were analyzed for oxygen content, blood gas tensions and pH. Cerebral blood flow was measured with a radioactively-labelled microsphere technique. Induced fetal hypoxaemia resulted in a metabolic acidaemia which was progressive over several h. Cerebral oxygen consumption was initially marginally decreased in response to induced hypoxaemia with cerebral blood flow increased thus maintaining O2 delivery coupled to cerebral oxygen consumption. With a worsening metabolic acidemia, pHa below 7.15, cerebral blood flow fell as mean arterial pressure fell, but cerebral oxygen consumption was little changed as fractional O2 extraction now increased. With sustained hypoxaemia and profound metabolic acidaemia, pHa below 7.00, fractional O2 extraction also fell resulting in a terminal fall in cerebral oxygen consumption to less than 50% of control values. Although the initial marginal decrease in cerebral oxygen consumption in response to induced hypoxia may represent a protective mechanism whereby the fetal brain decreases nonessential functions thus lowering oxidative needs, the terminal fall in cerebral oxygen consumption suggests pathological alterations within the brain at this time.

Animals↗