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Biomedical subjects

M D Jones

Publications and source records attributed to M D Jones.

At least 127 records · Page 7Linked to original sources

Neonatal uterine morphology as seen on real-time US.

The uterus in the neonate is prominent and readily identified on ultrasonography (US). The neonatal uterus is larger than the prepubertal uterus as a result of residual stimulation from maternal hormones. The uterus was visualized in 31 of 35 (89%) infant girls examined with real-time US. Mean uterine length was 3.4 cm. The majority of the uteri were tubular or spade-shaped, with the anteroposterior diameter of the cervix equal to or greater than the anteroposterior diameter of the fundus. The endometrial cavity was visualized in 30 (97%), a myometrial halo in nine (29%), and a small amount of endometrial fluid in seven (23%) of the uteri.

Cervix Uteri↗

Role of O2-hemoglobin affinity in the regulation of cerebral blood flow in fetal sheep.

Cerebral blood flow (CBF) and cerebral O2 transport (CBF X arterial O2 content) in the fetal sheep are nearly twice that in the adult, despite similar rates of cerebral O2 utilization. We tested the hypothesis that the difference depends on the increased oxyhemoglobin affinity in the fetus, using P50 (PO2 at which hemoglobin is 50% saturated) as the index of oxyhemoglobin affinity. We studied 18 unanesthetized fetal sheep in utero. In six animals the P50 was raised from 16.6 +/- 1.2 (SD) mmHg to 31.7 +/- 4.7 mmHg by exchange transfusing the fetus with adult sheep red blood cells. We measured CBF (with radioactive microspheres) and the PO2, PCO2, pH, and O2 content in carotid artery and sagittal sinus blood twice at the original P50 and twice after exchange transfusion. Arterial O2 content fell significantly at the higher P50. Since the fall in O2 content was not accompanied by a corresponding rise in CBF, O2 transport fell by 45%. Cerebral O2 consumption (CMRO2) did not change and cannot be implicated in the fall of O2 transport. E (the ratio CMRO2/O2 transport) rose by 77%. Sham exchange transfusions in six fetuses showed that the exchange transfusion procedure itself was not responsible for this alteration. To determine whether the fall in O2 transport and the rise in E was reproducible over a range of arterial O2 contents, a third group of six fetuses was studied. Fetal arterial O2 content varied from 4 to 12 vol%, first at P50 = 17 +/- 1.8 mmHg and again after exchange transfusion at P50 = 29.6 +/- 3.9 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of hematocrit on cerebral blood flow.

Cerebral blood flow (CBF) falls as hematocrit (Hct) rises. Investigators have differed on the relative importance of the increases in arterial O2 content (CaO2) and red blood cell concentration in mediating the fall. Our experimental protocol attempted to determine the independent effects of these two variables. In 13 unanesthetized lambs (less than 7 days old) we measured arterial and sagittal sinus blood gases, and O2 contents, and CBF (microsphere technique) at oxyhemoglobin Hcts of approximately 20 and 40% and after an isovolemic exchange transfusion with a mixture of normal and pure methemoglobin (MHb) containing red cells. Following MHb exchange, Hct rose (19.7 +/- 0.3 vs. 38.2 +/- 0.4%, mean +/- SEM) with little change in CaO2 (9.3 +/- 0.2 vs. 10.0 +/- 0.3 vol%). Arterial PCO2, pH, mean arterial blood pressure, and cerebral O2 consumption (CMRO2) did not change. However, CBF fell (153 +/- 11 vs. 110 +/- 7 ml . 100 g-1 . min-1). CBF declined further when CaO2 rose (17.3 +/- 0.5 vol%) at the higher oxyhemoglobin Hct (36.9 +/- 0.8%). We calculated that the increase in red cell concentration accounted for 56% of the decrease in CBF that ordinarily occurs as Hct rises from 20 to 40%. The effect of red cell concentration on CBF varied among individual animals. It correlated closely (r = -0.77) with the initial cerebral fractional O2 extraction [E = CMRO2/(CBF X CaO2)]. Animals with the most luxuriant O2 supply (CBF X CaO2) relative to demand (CMRO2) had the greatest decrements in CBF as red blood cell concentration rose.

Animals↗

Influence of reduced oxyhemoglobin affinity on cerebrovascular response to hypoxic hypoxia.

Increasing P50 (PO2 at 50% oxyhemoglobin saturation) reduces cerebral blood flow (CBF) during arterial normoxia. We tested the hypothesis that increasing P50 also diminishes the CBF response to isocapnic hypoxic hypoxia and that it reduces the response in proportion to the reduced normoxic CBF. P50 was increased in nine unanesthetized newborn lambs from 26.3 +/- 1.7 (+/-SE) to 36.6 +/- 2.0 Torr by isovolemic exchange transfusion with low-affinity, adult sheep blood. Microsphere-determined CBF was decreased 22% during arterial normoxia. The slope of the response curve to reduced arterial O2 content (CaO2) was proportionately attenuated by 26% with no change in O2 uptake. Consequently, O2 transport (CBF X CaO2) was reduced by a constant amount at each CaO2 level. The percentage decrease in CBF at the higher P50 was thus independent of CaO2, and the percentage increase in CBF as CaO2 fell was independent of P50: the effects of P50 and CaO2 were independent. Common to alterations in both P50 and CaO2 are alterations in capillary and tissue PO2. In this study the variable closest to capillary PO2 was sagittal sinus PO2. We found that when venous PO2 was altered by changing CaO2, the change in CBF was equivalent to that following the same alteration in venous PO2 after a change in P50. The percentage increase in venous PO2 after exchange transfusion was approximately one-half that of the increase in P50. About one-half of the potential increase in cerebral venous PO2 was therefore eliminated by a compensatory reduction in cerebral O2 transport over a wide range of CaO2.

Animals↗

Medical complications of prematurity.

The improved survival of extremely premature infants has generated intense interest in the quality of life of the survivors. This review focuses on the major long-term complications of prematurity (developmental disability, retinopathy of prematurity, chronic lung disease) and concludes with an overview of the broader spectrum of morbidity. Severe impairment (cerebral palsy, mental retardation, retrolental fibroplasia, severe chronic lung disease) fortunately occurs in a small proportion of survivors. However, the prevalence of the lesser morbidities (minimal cerebral dysfunction/learning disability, poor growth, postneonatal illnesses, rehospitalization) is less clearly defined. These problems all have an impact on families, and on medical and educational services.

Attention Deficit Disorder with Hyperactivity↗

Differentiation of transient hyperammonemia of the newborn and urea cycle enzyme defects by clinical presentation.

We reviewed clinical data in 33 patients with transient hyperammonemia of the newborn (THAN): six previously unreported cases and 27 from the literature. Thirteen neonates with urea cycle enzyme deficiencies (UCED) served for comparison. No differences were found in the incidence of perinatal complications, route of delivery, Apgar scores, sex, or incidence or time of onset of seizures. On the other hand, neonates with THAN had significantly lower birth weights (mean +/- SEM 2282 +/- 78 gm vs 3336 +/- 222 gm, P less than 0.001) and gestational ages (35.1 +/- 0.5 weeks vs 39.6 +/- 0.5 weeks, P less than 0.001). Mean time of onset of respiratory distress (3.9 +/- 1.4 hours vs 71.5 +/- 26.1 hours, P less than 0.001), ventilatory support (P less than 0.001), lethargy (P less than 0.005), and coma (P less than 0.005) occurred earlier in THAN. Distinctive laboratory findings in patients with THAN included abnormal chest radiographic findings and plasma ammonium concentrations that were higher (1871 +/- 209 microM vs 973 +/- 169 microM, P less than 0.02) at an earlier age. Respiratory distress occurred in all but one patient with THAN before 24 hours; in contrast, only 62% of infants with UCED had respiratory symptoms, and none before 30 hours. In this retrospective study, the clinical presentation alone differentiated THAN from UCED.

Amino Acid Metabolism, Inborn Errors↗

Regional blood flow and O2 transport during hypoxic and CO hypoxia in neonatal and adult sheep.

We compared regional blood flow in unanesthetized newborn lambs with that in adult sheep during acute, isocapnic hypoxic hypoxia [HH, 40-50% reduction of arterial O2 content (CaO2)]. The HH response in lambs and adults was qualitatively similar in heart, brain, and skeletal muscle, where flow increased; and in spleen, where it decreased. The response differed in skin and kidney, where flow decreased in lambs and was unchanged in adults, and in small intestine, where it was unchanged in lambs and increased in adults. Thus vasoconstriction during HH was less prominent in skin, kidney, and small intestine in adults. However, the trend toward lesser vasoconstriction in the adult cannot be attributed to a diminishing carotid chemoreflex and/or a more prominent vasodilatory lung inflation reflex because the same trend occurred during carbon monoxide hypoxia (COH). COH reduces CaO2 but stimulates neither the carotid chemoreflex nor, since hyperpnea is absent, the lung inflation reflex. Within each age group the responses to COH and HH were qualitatively the same. These data therefore provide no evidence for an active carotid chemoreflex in unanesthetized postnatal sheep. This is either because the peripheral circulatory effect of the chemoreflex is suppressed by the lung inflation reflex or, less likely, because the chemoreflex does not operate in the sheep at this level of HH.

Animals↗

Cerebrovascular hypoxic and autoregulatory responses during reduced brain metabolism.

The effect of reducing cerebral oxygen consumption (CMRO2) on the cerebral blood flow (CBF) responses to isocapnic hypoxic hypoxia and hypotension was examined in sheep. Newborn and adult animals were studied because of their different base-line CMRO2. Microsphere-measured CBF responses during pentobarbital coma (i.e., electroencephalographic silence) were compared with responses in conscious or lightly sedated animals. Induction of barbiturate coma reduced both CMRO2 and CBF by 50% from the awake value and by 25% from the value obtained in animals sedated with pentobarbital. The CBF response to 30 and 50% reductions in arterial O2 content (CaO2) was attenuated during coma, but only in proportion to the decrease in CMRO2. Whether CMRO2 was normal or reduced, the normoxic cerebral O2 delivery (CaO2 X CBF) was maintained during hypoxia in both newborns and adults. The relative autoregulatory index (fractional change in CBF divided by fractional change in perfusion pressure) was determined during graded hemorrhage. The index was not significantly different from zero (which represents perfect autoregulation) in awake, lightly sedated, or comatose animals. The data demonstrate that both base-line CBF and responses to hypoxia are closely tied to CMRO2 and that 50% reduction of CMRO2 does not impair cerebrovascular autoregulation.

Animals↗

Comparison of anterior cerebral artery blood flow velocity and cerebral blood flow during hypoxia.

Measurement of anterior cerebral artery blood flow velocity with a continuous wave bidirectional Doppler was compared with cerebral blood flow (CBF) measured with radioactive microspheres in 11 paralyzed newborn lambs during hypoxic hypoxia. The Doppler probe was maintained in a fixed position during each experiment. The objectives of the study were to validate this noninvasive technique that is being used widely in the clinical setting to qualitatively assess changes in CBF, and to evaluate which of the velocity parameters measured provide the most information. Diastolic velocity (DV), peak systolic velocity (PSV), area under the velocity curve (AUC), and pulsatility index (PI) were examined under conditions of varied arterial oxygen content and compared to microsphere CBF. DV (r = 0.72, p less than 0.001), AUC (r = 0.72, p less than 0.001), and PSV (r = 0.63, p less than 0.001) demonstrated stronger correlations with changes in CBF than did the PI (r = -0.41, p less than 0.05). DV (r = 0.81, p less than 0.001), AUC (r = 0.80, p less than 0.001), and PSV (r = 0.75, p less than 0.001) also exhibited stronger relationships with changes in arterial oxygen content than did the PI (r = -0.36, p less than 0.05). These data demonstrate that changes in cerebral blood flow velocity are useful qualitative measures of changes in cerebral blood flow. However, the utility of this technique is dependent upon a stable probe position, and assessment of the actual velocity measurements (DV, PSV, AUC) rather than simply the pulsatility index.

Animals↗

The effect of insulin on ovine fetal oxygen extraction.

Infusion of exogenous insulin (54 +/- 19 mU/kg/hr) to seven fetal lambs caused hyperinsulinism and arterial hypoxemia but not hypoglycemia. We measured the relationship between fetal oxygen delivery and oxygen use for a better understanding of the cause of the observed hypoxemia. Oxygen delivered to the fetus is the product of fetal umbilical venous oxygen content and umbilical blood flow. Both of these quantities decreased as fetal insulin concentration rose. The fall in umbilical blood flow was due to a change in the distribution of cardiac output. Cardiac output rose, but placental perfusion decreased while blood flow to the fetal carcass increased. Oxygen consumption by the ovine fetus increased as insulin concentration rose. Since the delivery of oxygen to the fetus did not increase when its use was rising, fetal extraction of available oxygen increased. Fetal arterial hypoxemia is the result of this increased extraction of available oxygen.

Animals↗

The EB virus genome in Daudi Burkitt's lymphoma cells has a deletion similar to that observed in a non-transforming strain (P3HR-1) of the virus.

Epstein-Barr virus (EBV) DNA isolated from the frequently studied and unusual Burkitt's lymphoma cell line, Daudi, contains a 7.4-kb deletion, similar to (but larger than) that found in a non-transforming isolate of the virus, P3HR-1. A comparison of EBV sequence in Daudi cells with that from a comparable region in a wild-type, transforming strain of the virus (B95-8) indicates that at least two of the previously identified RNAs, a highly repetitive sequence, and other interesting coding or structural features should be absent in Daudi EBV DNA as a consequence of the deletion. The information removed by the deletion, as well as that which might be generated by juxtaposition of two regions of the genome that are not adjacent in most strains of the virus are discussed.

Base Sequence↗

pFJ265, a new cloning vehicle for Streptomyces.

A 9.3-kb plasmid, pNM100, was isolated from Streptomyces virginiae (NRRL 15156) and characterized. Streptomyces genes for thiostrepton and neomycin resistance were cloned into pNM100 to yield a small plasmid derivative, pFJ265, that is suitable for Streptomyces gene cloning. pFJ265 is a 9.2-kb nonconjugative plasmid and has a copy number of several hundred per chromosome.

Chromosome Mapping↗

Comparison of cerebrovascular response to hypoxic and carbon monoxide hypoxia in newborn and adult sheep.

Cerebral blood flow (CBF) responses to two types of isocapnic hypoxia, hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH), were examined in seven unanesthetized adult sheep by the radiolabeled microsphere technique. Comparisons were made with newborn lambs (5-12 days old) previously studied under similar conditions. The arterial O2 content (CaO2) was reduced in a graded manner to 50-60% of the control value. During HH, CBF increased to maintain cerebral O2 delivery (CaO2 X CBF) in both adults and newborns; however, cerebral O2 uptake (CMRO2) did not change. Although CMRO2 was higher in newborns, the responses of CBF/CMRO2 to HH did not differ significantly in newborns and adults. In newborns, regional CBF showed that brainstem areas were particularly responsive to HH. In both age groups, CBF increased to a greater extent with COH than with HH for similar reductions in CaO2. This resulted in an increase in cerebral O2 delivery with COH. The degree to which COH differed from HH correlated with the magnitude of the leftward shift of the oxyhemoglobin dissociation curve that accompanies COH. In adults, CMRO2 fell by 16% with COH but was maintained in newborns. We conclude that maintenance of cerebral O2 delivery during acute, isocapnic HH is a property of CBF regulation common to both newborn and adult sheep. During COH, the position of the oxyhemoglobin dissociation curve is an additional factor that sets the level of O2 delivery. The fetal conditions of low CaO2 and a left-shifted oxyhemoglobin dissociation curve may have provided the newborn with a microcirculation better suited for maintaining CMRO2 during COH.

Animals↗

Retinal and choroidal blood flows in hypoxic and hypercarbic newborn lambs.

We studied the effect of changes in the arterial tensions of oxygen and carbon dioxide on blood flow to the retinal (RBF) and choroidal ( ChBF ) capillary beds in 20 lambs. One to three days after placement of catheters in the left ventricle, abdominal aorta, and brachiocephalic artery, different gas mixtures were delivered to a bag enclosing the lamb's head. One group of lambs was studied at normal and low oxygen tensions while normocarbic , and another group was studied at normal and high carbon dioxide tensions while normoxic. RBF and ChBF were measured using the radioactive microsphere technique. RBF increased as PaO2 and, thus, arterial oxygen content [( O2]a) fell; in contrast, ChBF was not related to [O2]a. Oxygen delivery to the capillary bed of the retinal artery (i.e., RBF X [O2]a) was independent of arterial oxygen content because the change in [O2]a was balanced by a reciprocal change in RBF. Oxygen delivery to the choroidal capillary bed, however, rose with [O2]a because there was no reciprocal decrease in ChBF . Both RBF and ChBF increase as arterial carbon dioxide tension rose. Although an increase in arterial carbon dioxide tension produced an increase in RBF with no change in [O2]a, oxygen delivery to the retinal capillaries rose. Similarly, oxygen delivery to the capillaries of the choroid rose with carbon dioxide tension. Oxygenation of retinal tissue, which depends on oxygen diffusion from both the retinal and choroidal capillary beds, may change with variations in arterial oxygen content (increase in oxygen delivered to the choroidal capillary bed) or arterial carbon dioxide tension (increase in oxygen delivered to both the retinal and choroidal capillary beds).

Animals↗

Distribution of cardiac output in fetal and neonatal lambs with acute respiratory acidosis.

The effects of changes in PaCO2 on the circulation are complex, involving local vasodilation, vasodilation mediated by the pulmonary inflation reflex, and vasoconstriction due to effects on central vasomotor centers and peripheral chemoreceptors. One might anticipate that some or all of these might differ between the fetus in utero and the newborn. Distribution of cardiac output was measured in unanesthetized fetal (n = 6) and newborn (n = 7) sheep, using the radioactive microsphere technique. PaCO2 rose from 44 to 70 (fetus) and 38 to 60 torr (newborn) with the addition of CO2 to room air. In the fetus, there were significant increases in central nervous system (CNS), diaphragm, and lung blood flows. No organ showed a significant decrease in flow. Local vasodilation by CO2 was the likely cause of the increased flow to CNS. The large increase in pulmonary blood flow was most likely due to the associated rise in fetal PaO2 (23 to 28 torr) that accompanied respiratory acidosis and the presence of fetal breathing movements. The rise in diaphragmatic blood flow was likely the result of fetal breathing. In the newborn, CNS and diaphragm flows rose, but unlike the fetus, spleen and stomach flows decreased. These decreased flows in the hypercapnic newborn may have been due to stimulation of either central vasomotor centers or peripheral chemoreceptors.

Acidosis, Respiratory↗

Carbonic acid dissociation constant (pK1) in critically ill newborns.

In the Henderson-Hasselbalch equation, the apparent first dissociation constant for carbonic acid in plasma, pK1, is 6.10 +/- 0.01 (+/- SD) in healthy adults. In contrast, values for pK1 in sick adults and in sick infants and children have been reported to vary widely. Because of the far reaching implications of these findings, we repeated the measurements in 19 newborns in a neonatal intensive care unit. Two measurements were made in each infant, one while the infant was acutely ill and another after recovery. We found that neither the mean value nor the range of pK1 values was affected by the infants' clinical status. The values during the acute phase of the hospitalization (range, 6.01-6.12; mean +/- SD, 6.08 +/- 0.03) did not differ from those after recovery (6.02-6.17; 6.08 +/- 0.04). A second study was performed in order to see if the wide range of pK1 values seen in other studies might be the result of an unstable state accompanying acute changes in acid-base status similar to those that might be encountered in clinical situations. However, data in seven lambs showed no significant difference when pK1 before an acute alteration in acid-base status (6.10 +/- 0.04) was compared with that 10 min after (6.09 +/- 0.03). In newborn intensive care units, nomograms are used to calculate total CO2 from pH and PCO2 assuming a pK1 = 6.10. Our data support this practice.

Acid-Base Equilibrium↗