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Biomedical subjects

M Fraser

Publications and source records attributed to M Fraser.

At least 91 records · Page 5Linked to original sources
PubMed1990

Correlation of absorbance at 650 nm with the presence of phosphatidylglycerol in amniotic fluid.

Amniotic fluid absorbance at 650 nm was correlated with the presence of phosphatidylglycerol (PG) in the isolated surfactant fraction (10,000-g pellet). Shake test results were included. Two hundred ninety-seven samples were analyzed. PG was present in 222 of 226 samples in which the absorbance was greater than or equal to 0.250 and absent from 48 of 71 with an absorbance less than 0.250. PG was present in all 166 samples with a positive shake test and absent in 52 of 131 samples with a negative one. In 65 samples in which the shake test was negative and the absorbance greater than or equal to 0.250, PG was present in all but 4. The false-positive rate for the prediction of respiratory distress syndrome was 0.8% for the Shake test and 0.6% for the absorbance measurement. The results support the usefulness of the absorbance measurement as a simple and reliable procedure for assessing fetal lung maturity.

Amniotic Fluid↗
PubMed1989

Structure of recombinant human renin, a target for cardiovascular-active drugs, at 2.5 A resolution.

The x-ray crystal structure of recombinant human renin has been determined. Molecular dynamics techniques that included crystallographic data as a restraint were used to improve an initial model based on porcine pepsinogen. The present agreement factor for data from 8.0 to 2.5 angstroms (A) is 0.236. Some of the surface loops are poorly determined, and these disordered regions border a 30 A wide solvent channel. Comparison of renin with other aspartyl proteinases shows that, although the structural cores and active sites are highly conserved, surface residues, some of which are critical for specificity, vary greatly (up to 10A). Knowledge of the actual structure, as opposed to the use of models based on related enzymes, should facilitate the design of renin inhibitors.

Aspartic Acid Endopeptidases↗
PubMed1989

Gestation-dependent effects of the combined treatment of glucocorticoids and thyrotropin-releasing hormone on surfactant production by fetal rabbit lung.

The effects of cortisol (0.1 mg per dose, administered intraperitoneally to fetal rabbits at 24 to 27 days' gestation), thyrotropin-releasing hormone (40 micrograms/kg per dose administered intravenously to the doe at 24 to 26 days' gestation), or a combination of the two on surfactant pool size (both intracellular and extracellular) at 27 or 28 days' gestation was investigated. Cortisol increased both surfactant pools only when administered on the twenty-fourth or twenty-fifth gestational day. Thyrotropin-releasing hormone, whether administered in single or multiple doses, had no effect on the extracellular pool but increased the intracellular pool; the magnitude of the response (approximately twofold) was similar to that observed with the cortisol response. All combinations of cortisol and thyrotropin-releasing hormone resulted in an increased response over either drug given alone. The greatest response (almost tenfold) resulted from cortisol administration at 24 days' gestation plus thyrotropin-releasing hormone administration at 24+ 25+ 26 days. These data demonstrate differential effects of glucocorticoids and thyrotropin-releasing hormone on developing lung and furthermore show that the timing of their combined treatment may be crucial to achieving maximal response.

Animals↗
PubMed1989

The effect of cortisol on thyroid hormone kinetics in the ovine fetus.

The mechanism underlying the association of rising concentrations of circulating triiodothyronine (T3) with the prepartum surge in the concentration of cortisol was investigated in 11 fetal sheep. The concentrations and metabolic clearance rates of T3 and thyroxine (T4) were measured prior to and following a continuous intravascular infusion of cortisol (1 mg/h for 84 h). Mean plasma T3 concentrations increased 10-fold following cortisol infusion whereas the concentrations of T4 either remained stable or exhibited a variable decline. Cortisol induced a 5-fold decrease in the metabolic clearance rate of T3 and a 6-fold increase in that of T4. The corresponding mean production rates of T3 and T4 increased significantly although the magnitude of the change varied between fetuses. We conclude that the prepartum rise in plasma T3 concentrations is likely to be a consequence of both a decreased metabolic clearance of T3 and increased peripheral conversion of T4 to T3 caused by rising concentrations of cortisol in fetal plasma.

Animals↗
PubMed1988

Umbilical cord knots and encirclements.

Although cord knots and/or encirclements account for 1 in 10 stillbirths of infants weighing 2,500 g or more, no problem due to this cause was encountered in a prospective study of 1,115 vaginal deliveries. In this study there were 6 cases of cord knot (0.5%) and 158 of cord encirclement (14.2%). The range of cord length was 27-122 cm, the 10th, 50th and 90th percentiles being 40, 52 and 69 cm respectively. In this study there was no clinical warning (fetal distress) of cord encirclement or knot during pregnancy, labour or delivery.

Asphyxia Neonatorum↗
PubMed1988

Cardiovascular effects of the novel cardiotonic agent DPI 201-106 in the anaesthetized rat.

DPI 201-106 (4-[3-(4-diphenylmethyl-1-piperazinyl)-2-hydroxypropoxy]-1H-indole -2- carbonitrile) was given intravenously to anaesthetized male rats. DPI caused an increase in left ventricular dP/dt (LV dP/dt), giving a significant increase at 0.03 mumol/kg. At this dose DPI had no effect on either mean arterial pressure (MAP) or heart rate (HR). At higher doses, MAP decreased transiently. At 0.3 and 1 mumol/kg, HR was decreased. The results indicate that DPI produces positive inotropic and negative chronotropic effects in the anaesthetized rat.

Animals↗
PubMed1988

Inhibition of cardiac phosphodiesterase III by the novel cardiotonic agent 6-[4-(4'-pyridyl)aminophenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride.

The novel cardiotonic agent 6[4-(4'-pyridyl)aminophenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride (MCI-154) was investigated for its cardiovascular effects and its mechanism of action. In the anaesthetized rat MCI-154 (0.01-0.3 mumol/kg i.v., bolus injection) produced a dose-dependent increase in left ventricular dP/dt, and a decrease in mean arterial pressure. A relatively small increase in heart rate was observed. The drug inhibited selectively canine cardiac phosphodiesterase III (IC50 2.5 +/- 0.6 mumol/l). In skinned porcine trabeculae, MCI-154 produced only a small increase in the Ca2+-sensitivity of the contractile proteins. The results suggest that MCI-154 is a potent cardiotonic agent, and that inhibition of phosphodiesterase III may be a important component of this effect.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Thyroid hormone kinetics during late pregnancy in the ovine fetus.

The factors responsible for the changes in the plasma concentrations of thyroid hormones in the ovine fetus in late pregnancy were investigated by making serial measurements of the concentrations, metabolic clearance rates and production rates of T3 and T4 in 17 fetuses. The concentrations of T3 in fetuses of 135-145 days gestational age were four times higher than in those of 110-125 days but the concentrations of T4 were unchanged. The metabolic clearance rate of T3 halved over this period whereas that of T4 rose slightly. The production rate of T3 more than doubled and of T4 increased slightly but not significantly. We conclude that the concentration of T4 shows little change with increasing gestational age because the trends in metabolic clearance rates and production rates are weak and in the same direction. The sharp rise in the concentration of T3 is attributable to a fall in metabolic clearance rate coupled with a rise in production rate.

Animals↗
PubMed1987

Diagnosis of gestational diabetes by capillary blood samples and a portable reflectance meter: derivation of threshold values and prospective validation.

Paired capillary-venous samples were obtained from 255 women undergoing a glucose challenge test and 116 women undergoing an oral glucose tolerance test. The capillary equivalents for the venous threshold values were calculated by regression analysis. The glucose challenge test predictions of either normal or abnormal agreed in 82%. The sensitivity, specificity, and positive and negative predictive values for the capillary oral glucose tolerance test were 89%, 90%, 62%, and 98%, respectively. These capillary equivalents were then applied prospectively to 147 women undergoing a glucose challenge test and 141 women undergoing an oral glucose tolerance test. The concurrence rate of the glucose challenge test in the prospective group was 90%. The sensitivity, specificity, and positive and negative predictive values for the capillary oral glucose tolerance test were 64%, 95%, 75%, and 92%. When the venous threshold recommendations of the American Diabetes Association were used instead of those standard at our institution, these values increased to 75%, 98%, 83%, and 96%, respectively. The recommended capillary values of the American Diabetes Association were 100% sensitive but had a positive predictive value of only 20%. Based on the prospective group, the cost per case of gestational diabetes identified would decline 63% if both a capillary glucose challenge test and an oral glucose tolerance test were used and 25% if the capillary glucose challenge test and venous oral glucose tolerance test were used. Combining the data set for new regression equations, the following venous-capillary threshold sets emerged: glucose challenge test, 140 mg/dl/150 mg/dl; fasting oral glucose tolerance test, 105 mg/dl/114 mg/dl; 1 hour, 190 mg/dl/211 mg/dl; 2 hours, 165 mg/dl/183 mg/dl; 3 hours, 145 mg/dl/157 mg/dl. The sensitivity, specificity, and negative predictive values for the capillary oral glucose tolerance test with these thresholds were 80%, 97%, 80%, and 97%. In conclusion, capillary glucose testing for diabetes during pregnancy is feasible and cost-effective.

Blood Glucose↗
PubMed1986

The relationship between capillary and venous glucose concentration during pregnancy.

Previous attempts to construct capillary equivalents of venous glucose values for prognostic purposes have failed. We examined the relationship between capillary and venous glucose concentration during pregnancy in 258 women who had samples taken at four different time intervals in relation to two different standardized meals. Capillary glucose concentration was determined with the Chemstrips bG and an Accu-Chek reflectance colorimeter and venous plasma glucose concentration was measured by the hexose kinase technique on an AutoAnalyzer. The capillary: venous relationship was constant over time for a given meal but the magnitude of the difference was affected by time. The capillary: venous relationship differed significantly between the two standard meals. The findings indicate that meal size and sampling time must be controlled for when one is attempting to construct capillary equivalents for venous derived norms. The failure of previous studies to control for these variables may explain their inability to construct useful capillary equivalents for venous glucose values. Our findings also indicate that attainment of venous norms with capillary specimens represent, in reality, tighter control.

Blood Glucose↗
PubMed1986

Quantification of surfactant pool sizes in rabbit lung during perinatal development.

Methods are presented for the quantitative isolation of surfactants from fetal and newborn rabbit alveolar lavage returns and post-lavaged lung tissue homogenates. The phospholipid content of both fractions progressively increased between 27 days gestation and term (31 days). The tissue-stored fraction increased approximately 16-fold (from 0.48 +/- 0.13 to 7.83 +/- 0.86 mg/g dry lung) and the alveolar fraction more than 30-fold (from 0.08 +/- 0.02 to 2.69 +/- 0.52 mg/g dry lung). Developmental changes in phospholipid composition were also observed. Tissue-stored surfactant was prepared using differential and density gradient centrifugation. Alveolar surfactant was isolated during fetal development as a high-speed pellet following a one-step differential centrifugation. There was little change in the phospholipid content of fetal alveolar lavage supernatant (range 0.12 +/- 0.04 to 0.28 +/- 0.09 mg/g dry lung). By the first postnatal day the phospholipid content of both lavage fractions significantly increased (pellet, 7.51 +/- 1.79; supernatant, 4.01 +/- 1.36 mg/g dry lung) and both were identified as surfactant. This increase in alveolar surfactant was accompanied by an approximately twofold decrease (to 3.81 +/- 1.1 mg/g dry lung) in the tissue-stored fraction. These data provide a quantitative profile of surfactant accumulation and secretion in developing rabbit lung.

Animals↗
PubMed1985

Circulating thyrotropin in the ovine fetus: evidence for pulsatile release and the effect of hypothermia in utero.

The secretion of thyrotropin (TSH) has been investigated in the chronically catheterized ovine fetus (term 145-150 days). Forty-two random plasma samples from 25 fetuses (86-149 days of gestation) were measured for TSH concentrations by radioimmunoassay. Plasma TSH concentrations were highest in the youngest fetuses [86-110 days, 3.9 +/- (SD) 5.5 microU/ml, n = 13]. Thereafter TSH concentrations declined to 0.4 +/- 0.6 microU/ml (n = 13, p less than 0.05) at 130-150 days of gestation. However, serial sampling at 15-20 min intervals for 180 min from 14 individual fetuses (91-139 days) showed that TSH was secreted in a markedly exaggerated pulsatile manner compared to that observed after birth. The mean amplitude of TSH pulses fell (p less than 0.005) from 5.9 +/- 8.1 microU/ml in the fetuses to 2.1 +/- 1.1 microU/ml in five neonatal lambs (6-22 days) and to 1.5 +/- 0.4 microU/ml in three adult nonpregnant ewes. The mean pulse frequency for the 14 fetuses was 0.7 +/- 0.3 pulses/h and was reduced (p less than 0.001) to 0.3 +/- 0.1 pulses/h in lambs and to 0.3 +/- 0.1 pulses/h in the ewes. In the neonate, hypothermia is a potent stimulus to TSH release. To examine the ontogeny of this response, the temperature of the fetus in utero (106-127 days of gestation) was lowered by circulating water (14-18 degrees C) at either a fast or slow rate through a coil placed either externally around the fetus or internally in the fetal esophagus and stomach.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Trochanteric advancement for premature arrest of the femoral capital growth plate.

Premature closure of the growth plate of the femoral capital epiphysis associated with limitation of abduction and gluteal insufficiency is described. The indications for trochanteric advancement and the results obtained in the late treatment of Perthes' disease and of congenital dislocation are discussed. Nine hips treated after Perthes' disease had satisfactory results, in that all were improved; but in eight hips with deformity arising from congenital dislocation the outcome was less favourable.

Adolescent↗
PubMed1985

Unstable fractures of the thoracolumbar spine: a 10-year experience at Sacré-Coeur Hospital.

UNLABELLED: In a 10-year period, 108 unstable fractures involving the thoracolumbar junction (T11 to L2) were treated. This study evaluates the influence of the different treatments on the rate of complication, reduction of the fracture, and neurological recovery. METHODS: mechanism of injury, initial treatment and delay, neurologic deficit, operative findings, and duration of hospitalization were recorded. X-rays were reviewed for classification of fracture, measurement of deformity, and for instability scoring according to White and Panjabi's criteria. Seventy-seven patients were examined and nine more interviewed by telephone. RESULTS: a flexion-rotation injury occurred in 65% and a burst-fracture in 29%. A laminectomy was performed in 30 patients and Harrington instrumentation and fusion in 71 patients. Sixteen patients were treated conservatively. Fifty-five patients presented either a complete or partial neurological deficit. Seventy-five complications were noted and were more frequent in the laminectomy group. The instrumented group showed a clear tendency for earlier ambulation and discharge and pain level was found to be less. An increased residual deformity was found in patients treated by laminectomy, short fusion, and by nonsurgical modality. The neurologic recovery in the laminectomy and the nonlaminectomy group was not significantly different. Spinal realignment was better in the group where an instrumentation of five levels or more was performed and where posterior elements were not removed by laminectomy.

Adolescent↗
PubMed1985

Haemodynamic and catecholamine responses to hypothermia in the fetal sheep in utero.

Chronically catheterised fetal sheep (117-134 days) were cooled in utero via a tubing coil placed around the fetal trunk through which cold water was circulated for one hour. The fetal core temperature was reduced by 5.51 +/- 0.61 degrees C. This hypothermia was associated with tachycardia (P less than 0.001) and hypertension (P less than 0.001) (n = 12). The tachycardia was abolished by treatment with propranolol (n = 4) and the hypertension by treatment with phentolamine (n = 5). Blood flow in the left umbilical artery was measured by an electromagnetic flow probe in 4 fetuses and rose (P less than 0.001) with fetal cooling. The increase in blood flow was abolished by treatment with either phentolamine or propranolol. These observations are consistent with a redistribution of fetal blood flow from peripheral tissues to placental and thermogenic tissues during cooling. Fetal plasma adrenaline and noradrenaline concentrations rose (P less than 0.01) during fetal cooling (n = 5). These studies demonstrate that catecholamine and cardiovascular responses to environmental hypothermia have differentiated prior to birth in the sheep fetus.

Animals↗