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Biomedical subjects

R Natale

Publications and source records attributed to R Natale.

At least 37 records · Page 2Linked to original sources

Multicenter phase II study of brequinar sodium in patients with advanced gastrointestinal cancer.

Eighty-six patients with advanced colorectal, gastric or pancreatic carcinoma and no prior exposure to chemotherapy were treated with brequinar sodium. Brequinar was administered at a median weekly dose of 1200 mg/m2 intravenously. The toxicity was moderate, with thirty patients (35%) experiencing grade 3 or 4 toxicity. Objective responses were observed in 1/32 evaluable colorectal and 2/29 evaluable gastric carcinoma patients. There were no objective responses in 17 evaluable pancreatic cancer patients. We conclude that, at this dose and schedule, brequinar does not have sufficient activity in these gastrointestinal malignancies to warrant further evaluation.

Adult↗

Multicenter phase II trial of brequinar sodium in patients with advanced melanoma.

Seventeen patients with advanced melanoma and no prior exposure to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given at a median weekly dose of 1200 mg/m2 intravenously. In 14 patients evaluable for efficacy, there were no objective responses. The toxicity was moderate. We conclude that, at this dose and schedule, brequinar has no activity in advanced melanoma.

Adult↗

Is perinatal care in southwestern Ontario regionalized?

OBJECTIVE: To determine whether perinatal care in southwestern Ontario is regionalized, to identify trends over time in referral patterns, to quantify trends in perinatal death rates and to identify trends in perinatal death rates that give evidence of regionalization. DESIGN: Cohort study. SETTING: Thirty-two hospitals in southwestern Ontario (1 level III, 1 modified level III and 30 level II or I). PATIENTS: All pregnant women admitted to the hospitals and their infants. MAIN OUTCOME MEASURES: Antenatal and neonatal transfer status, live-born with discharge home alive from hospital of birth, stillborn, and live-born with death before discharge. RESULTS: Between 1982 and 1985 the antenatal transfer rate increased from 2.2% to 2.8% (p less than 0.003). The proportion of births of infants weighing 500 to 1499 g increased from 49% to 69% at the level III hospital. The neonatal transfer rate increased from 26.2% to 47.9% (p less than 0.05) for infants in this birth-weight category and decreased from 10.2% to 7.1% (p less than 0.03) for infants weighing 1500 to 2499 g. The death rate among infants of low birth weight was lowest among those born at the level III centre and decreased at all centres between 1982 and 1985. CONCLUSIONS: Perinatal care in southwestern Ontario is regionalized and not centralized; regionalization in southwestern Ontario increased between 1982 and 1985.

Female↗

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↗

Maternally perceived fetal activity from twenty-four weeks' gestation to term in normal and at risk pregnancies.

Maternal perception of fetal activity was studied in normal and at risk pregnancies from 24 weeks' gestation until term in the second and third hour after a maternal meal. The trend for the median number of maternally perceived fetal movements in the 2-hour observation period, across gestation, was similar to that previously reported in both maternally perceived and ultrasound studies. The median number of perceived fetal movements in any 15-minute interval was similar for both groups and was constant over gestational age. The periodicity of fetal activity perceived by mothers correlated well with ultrasonic observations. The data support that fetal movement counts are very variable. Periodicity must be taken into account when maternally perceived fetal activity is used as a screen of fetal well-being. The data suggest that the patient should be observed for a consecutive period, up to a maximum of 2 hours. If no fetal activity is perceived by 2 consecutive hours of observation, then further evaluation of fetal well-being should be considered.

Female↗

Ultrasonic evaluation of fetal body movements over twenty-four hours in the human fetus at twenty-four to twenty-eight weeks' gestation.

Continuous 24-hour observations of fetal gross body movements were performed in 20 women between 24 and 28 weeks of gestation by means of real-time ultrasound examination. At 24 to 26 weeks, fetuses moved 13.1% +/- 0.3% of the time, which was not significantly different from the incidence of 12.4% +/- 0.8% at 26 to 28 weeks' gestation. An examination of the number of movements per hour demonstrated that fetuses at 24 to 26 weeks' gestation moved on the average 53.4 +/- 1.6 times/hr, which was significantly different from 26 to 28 weeks' gestation when fetuses made 46.2 +/- 1.4 movements/hr. When examined on an hourly basis, fetuses in both age groups demonstrated a significant increase in the number of movements overnight from 2300 to 0800 hours. Intermovement intervals were also examined. Ninety-nine percent of intervals less than 6 minutes in both age groups contained movement. The longest observed quiescent interval was 24 minutes in both age groups. These data suggest that the incidence of fetal body movements is different than that observed in fetuses during the last 10 weeks of gestation. Fetuses at 24 to 28 weeks' gestation exhibit a diurnal pattern of fetal movement and move more frequently than do older fetuses. However, these movements are of a sporadic nature and relatively short duration. Thus these fetuses do not appear to have well-defined periods of rest and activity.

Circadian Rhythm↗

Patterns of fetal breathing activity in the human fetus at 24 to 28 weeks of gestation.

Continuous 24-hour observations of fetal breathing were performed in 20 normal, pregnant women between 24 and 28 weeks' gestation by real-time ultrasound. Fetuses made breathing movements approximately 14% of the time. No change in breathing activity after a maternal meal was observed, but a significant increase in the incidence of fetal breathing activity was noted overnight. Fetuses at 24 to 28 weeks' gestation breathed at a rate of 44 breaths per minute, and the longest period of apnea noted was 14 minutes. These data suggest that the pattern and incidence of fetal breathing at 24 to 28 weeks' gestation are different from those of fetuses observed in the last 10 weeks of pregnancy. A maturational process in the control of fetal breathing may explain these observations.

Adult↗

The role of carbon dioxide in the generation of human fetal breathing movements.

To determine the role of carbon dioxide in the generation of fetal respiratory movements, the effect of induced maternal hypocapnia and hypercapnia on fetal breathing movements, gross body movements, and fetal heart rate was studied in 12 healthy pregnant women near term. Patients were studied for a 1-hour control period breathing room air followed by four randomized 15-minute study periods with patients breathing either room air, a prepared gas mixture with 2% or 4% carbon dioxide, or undergoing controlled hyperventilation as determined by monitoring end-tidal PCO2. The percentage of time fetal breathing movements correlated significantly with maternal end-tidal PCO2 (r = 0.62, p less than 0.01), increasing with maternal breathing of 2% and 4% carbon dioxide and decreasing with maternal hyperventilation. Fetal gross body movements, fetal heart rate, and fetal heart rate variability showed no significant changes. It is concluded that as in adults, the carbon dioxide level in fetuses is an important stimulus for the generation of respiratory movements, acting independent of a change in behavioral state. It is hypothesized that tonic carbon dioxide level input is an important determinant of fetal respiratory center drive, but little or no phasic carbon dioxide input exists because of continuous placental excretion, thus resulting in the episodic occurrence of breathing movements with changes in the fetal behavioral state.

Adult↗

Monoclonal antibody (5G6.4) against ovarian carcinoma shows inhibition of in vitro colony formation.

Monoclonal antibodies (MAbs) have the potential for diagnosis and therapy of cancer, 5G6.4 is a MAb of the IgG2a class which was produced by immunization of BALB/c mice with human ovarian carcinoma (Ov Ca) cells. To further characterize 5G6.4, its effect on cell growth was tested using a human Ov Ca cell line established in our laboratory. A clonogenic assay was set up in 48-well plates in a double agar system. The cells were plated and 5G6.4 was added at different concentrations. Control plates consisted of cells with media without MAb. Negative control plates were also prepared using the same concentrations of an isotype-matched antimelanoma MAb, 225.28s. Colony formation (CF) was reduced to 50% or less of control with increasing amounts of 5G6.4 up to 50 micrograms/ml. Although CF was still depressed at concentrations above 50 micrograms/ml, the inhibition did not follow a directly proportional line; instead, it followed a bell-shaped curve. Plates with the control MAb, 225.28s, did not show this response. Similar results were obtained with cells from malignant Ov Ca ascites in the same clonogenic assay. Our study suggests that in the evaluation of the in vitro effect of MAb on growth, the concentration of MAb is crucial and may not show a linear response and that 5G6.4 may have a direct therapeutic effect by blocking the growth of Ov Ca cells. 5G6.4 is presently under study for therapy in an animal model.

Antibodies, Monoclonal↗

The effect of electrical stimulation on behavioral states in the fetal lamb.

Brachial nerve stimulation at two frequencies (0.01 and 0.05 pulse per second, pps) with the fetus in either low-voltage electrocortical activity with eye movements or high-voltage electrocortical activity without eye movements was studied in five chronically catheterized fetal lambs at 130 to 140 days' gestation. During low-voltage electrocortical activity with eye movements, there were slight alterations in electrocortical state and electromyographic activity at 0.01 pps. At 0.05 pps these electromyographic changes were enhanced above those expected as a result of state changes but returned to control values during the recovery period. During high-voltage electrocortical activity without eye movements, the state changes were much more dramatic, while electromyographic activity increased significantly only at 0.05 pps. It was of note that in both high- and low-voltage electrocortical activity the fetal heart rate changed only during the recovery period at 0.05 pps. It is concluded that fetal behavioral state influences the interpretation of biophysical measurements in the fetus and that the effect of stimulation is more pronounced if applied when the fetus is in high-voltage electrocortical activity without eye movements.

Animals↗

Fetal megaureters masquerading as bowel obstruction.

As a result of repeated ultrasound assessments for determination of gestational age, more congenital anomalies are detected in the fetus. Early diagnosis has serious implications for both mother and fetus. We present our experience in the management of a male fetus with obstructive uropathy diagnosed at seventeen weeks of gestation. In serial ultrasounds the tortuous megaureters were mistaken for distended loops of bowel. When the question of obstructive uropathy is raised, and the bladder cannot be visualized, administration of diuretics to the mother may promote fetal bladder filling. Since the advent of intrauterine surgical intervention, distinguishing between megaureters and obstructive bowel disease may have important clinical implications.

Diagnostic Errors↗

Longitudinal measurements of fetal breathing, body movements, heart rate, and heart rate accelerations and decelerations at 24 to 32 weeks of gestation.

Fetal breathing, fetal body movements, fetal heart rate, and fetal heart rate accelerations and decelerations were studied longitudinally in healthy fetuses between 24 and 32 weeks' gestation in the second and third hour following an 800 kcal maternal meal. The expected increase in fetal breathing following a maternal meal was not seen until fetuses were at 30 to 32 weeks' gestation. The number of body movements decreased and the interaction between body movements and fetal heart rate accelerations became more evident as fetuses became older. Fetal heart rate decelerations increased with gestational age, and the relative proportion of total decelerations that were either associated with body movements or were part of a deceleration/acceleration/deceleration complex increased from 24 to 32 weeks' gestation. The data support the hypothesis that gestational age is an important variable to consider when interpreting biophysical measurements in the human fetus at 24 to 32 weeks' gestation. Fetal body movements may be the single most important measurement of fetal health at these gestational ages.

Adult↗

The relationship between movements and accelerations in fetal heart rate at twenty-four to thirty-two weeks' gestation.

The purpose of this study was to establish the relationship between fetal heart rate accelerations and fetal body movements in fetuses at 24 to 32 weeks' gestation. The results suggest that body movements in younger fetuses do not occur with accelerations that are readily recognizable (i.e., less than 15 bpm), but as fetuses get older, the interaction between body movements and fetal heart rate becomes more evident and accelerations become more recognizable (i.e., greater than or equal to 15 bpm). The data presented suggest that there is a maturational aspect to the relationship between fetal heart rate and fetal body movements as fetuses increase in gestational age from 24 to 32 weeks. The conclusion, therefore, is that the nonstress test, as presently defined for older fetuses, is not valid for gestations below 32 weeks, and new criteria must be established.

Female↗

Does adrenal cortex influence prolactin secretion? Evaluation in hirsute women.

To define the role of adrenal hormones on PRL secretion, we investigated 28 women by administering i.v. 0.25 mg. ACTH (h 8.00) every 45' for 135' to better evaluate any relationship between enhanced adrenal steroidogenic activity (both glycoactive and androgenic) and PRL secretion. Blood samples were drawn at 0', 45', 90', 135', and PRL, F, DHEAS, and 170HP were measured by RIA methods. A significant lowering of PRL levels and a concomitant enhancement of steroid plasma levels were found. Our data are in line with those found by some Authors who observed the lack of PRL enhancement after hypoglycemia during glucocorticoid administration and the absence of nocturnal peak of PRL in patients with Cushing's disease. However statistical evaluation (linear analysis regression) of data obtained provides further evidence for the extremely influential role played by adrenal gland hormones on PRL secretion in women.

Adrenal Cortex↗

Importance of serum androgens chromatography on the acth stimulated adrenal steroidogenesis evaluation in hirsute women.

20 hirsute women ageing between 13-38 and 10 age matched controls were investigated. Steroid pattern (F, 170HP, T, DHEAS, A, DHT) were evaluated after repetitive ACTH administration (0.25 mg every 45' for 135'). Testosterone was assayed either directly in ether serum extract (T) or after a previous silica-gel thin layer chromatography (Tc). Basal serum values of all steroids under investigation were significantly higher in hirsute women than in controls. T values resulted higher than Tc thus stressing the high degree of cross-reactivity among DHT, DHEAS, A and T in unchromatographed serum steroid RIA. On the other hand ACTH repeated administration elicited an earlier and more significant T value increase in normals than in hirsutes, whereas Tc did not show any significant change in either group. Similarly DHT serum values did not vary after repetitive ACTH administration either in controls or in hirsute women. During ACTH test A serum values enhanced at 45' in both controls and hirsute women without any further increase after ACTH injections, whereas a lower degree of DHEAS enhancement during ACTH test was observed. On the contrary both F and 17-OHP plasma values strongly enhanced at 45' but a further increase of their values after every ACTH stimulus was also observed. Our data seem to confirm the enhanced adrenal steroidogenesis in hirsutism. But the adrenal contribution to enhanced androgen serum pattern of hirsute women appears to be more evident in androstenedione than in the testosterone fraction.

Adolescent↗