1757--year of failure and tragedy.
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Biomedical subjects
Publications and source records attributed to B Richardson.
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The disposition of ethanol in maternal arterial blood, fetal arterial blood, and amniotic fluid of nine conscious, cannulated pregnant ewes (128 to 137 days' gestation) was determined for 1-hour maternal intravenous infusion of ethanol, 1 gm/kg maternal body weight. The maternal arterial blood and fetal arterial blood ethanol concentration-time curves were virtually superimposable up to 14 hours. The apparent zero-order ethanol elimination rates for maternal arterial blood and fetal arterial blood were similar. There was a time lag in the transfer of ethanol into amniotic fluid relative to fetal arterial blood, and the peak ethanol concentration in amniotic fluid was significantly lower than the concentrations in maternal arterial blood and fetal arterial blood. The apparent zero-order ethanol elimination rate for amniotic fluid was slower, but not significantly so, compared with the ethanol elimination rates for maternal arterial blood and fetal arterial blood. Ethanol-derived acetaldehyde was found in maternal arterial blood, fetal arterial blood, and amniotic fluid at concentrations at least 1000-fold lower than the respective ethanol concentrations. The data indicate that, for administration of this ethanol dosage regimen to the third-trimester pregnant ewe, there is rapid, bidirectional placental transfer of ethanol; elimination of ethanol from the fetus is regulated primarily by maternal elimination of ethanol; the amniotic fluid may serve as a reservoir for ethanol in utero; and there is appreciable acetaldehyde-metabolizing capacity.
Ethanol (1 gm/kg of maternal body weight administered over 1 hour) was infused intravenously into 11 chronically prepared pregnant ewes between 128 to 137 days' gestation. Fetal breathing movements were suppressed for 9 hours following ethanol administration, and both high- and low-voltage fetal electrocortical activity were suppressed for 3 hours and replaced by intermediate-voltage electrocortical activity. Fetal blood gases and pH were not altered. These data support the hypothesis that ethanol suppresses fetal breathing movements by a direct central mechanism rather than indirectly by alteration of electrocortical activity.
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The contractile effect of 5-HT in the isolated longitudinal ileal muscle of adult guinea-pigs was studied over a large concentration range. 5-HT produced a biphasic concentration-response curve indicative of an interaction with at least two independent populations of receptors. The concentrations which elicited half-maximal effects for the first and the second phases of the concentration-response curve were estimated as 1.5 +/- 1.2 X 10(-8) mol/l and 1.3 +/- 0.4 X 10(-6) mol/l respectively. The maximal response produced by the interaction of 5-HT with the high affinity receptor (i.e. first phase) was calculated as 27 +/- 9.3% of the total response. The biphasic concentration-response was not influenced by methysergide (10(-6) mol/l). The effect of low concentrations of 5-HT (less than 3 X 10(-7) mol/l) was antagonised by atropine (10(-7) mol/l), tetrodotoxin (TTX) (10(-6) mol/l), morphine (10(-5) mol/l), the substance P antagonist, D-Pro4,D-Trp7,9-SP4-11 (3 X 10(-5) mol/l) and capsaicin (10(-5) mol/l). Physostigmine (10(-7) mol/l) augmented the effect. The response to high concentrations of 5-HT (3 X 10(-7)-3 X 10(-6) mol/l) was antagonised by ICS 205-930 and D-Pro4,D-Trp7,9-SP4-11 in a competitive manner and was inhibited by TTX, morphine and capsaicin in an insurmountable way. The effect of very high concentrations of 5-HT (greater than 10(-5) mol/l) could be partially antagonised by methysergide (10(-7) mol/l) in the presence of ICS 205-930 (10(-7) mol/l) and totally by a combination of methysergide and TTX.(ABSTRACT TRUNCATED AT 250 WORDS)
To evaluate the role of cisplatinum in the treatment of advanced non-small cell lung cancer, 48 patients received either a doxorubicin (adriamycin) 50 mg/m2 I.V., cyclophosphamide 300 mg/m2 I.V., lomustine (CCNU) 50 mg/m2 p.o., vincristine (oncovin) 1.2 mg/m2 I.V. (ACCO) combination or the same drugs plus cisplatinum 50 mg/m2 I.V. (PACCO) in a prospective sequential trial. No patient had received prior chemotherapy. Patients receiving the two regimens were comparable with regard to median age, performance status, histologic subtype, disease extent, and weight loss. Objective response frequency was only 5% in the initial 20 patients receiving ACCO treatment compared to a response frequency of 28% (7% complete) in the 28 patients receiving cisplatinum in the PACCO treatment arm (p less than 0.06). Patients achieving objective response lived significantly longer than nonresponders (9.1 months vs. 3.8 months, p less than 0.05). Although median survival was similar on the two regimens (6.1 months for ACCO vs. 7.6 months for PACCO), more than four times as many patients were alive after 1 year in the PACCO treatment group (24% vs. 5%). Predominant toxicity consisted of moderately severe nausea and vomiting (63% on PACCO vs. 34% on ACCO, p less than 0.05) and myelosuppression with WBC less than 3,000/mm3 occurring in the majority of patients on both regimens. These results suggest cisplatinum addition to a doxorubicin, cyclophosphamide, lomustine, and vincristine combination may be associated with increased 1-year survival in the non-small cell lung cancer patient population.
Thirty-eight patients with advanced cancer and weight loss were tested in a prospectively randomized, double-blind, placebo-controlled trial to evaluate the influence of hydrazine sulfate on carbohydrate metabolism in cancer cachexia. All patients had an initial 3-day inpatient metabolic evaluation including: standard 5-hr p.o. glucose tolerance test, hormone studies, and total glucose production by infusion of [6-3H]glucose. After 30 days of treatment with capsules containing either placebo or hydrazine sulfate in a 60-mg, 3 times/day dosage, inpatient evaluation was repeated. A total of 62 metabolic inpatient evaluations were performed. The pretreatment characteristics of age, sex, prior therapy experience, nutritional parameters and tumor types were comparable in placebo and hydrazine treatment groups. On initial evaluation, abnormal glucose tolerance and increased glucose production were frequently seen. Serial assessment of glucose tolerance showed no improvement after 30 days of placebo treatment. However, the glucose tolerance was significantly improved in patients receiving 30 days of hydrazine sulfate [2-hr glucose; initial 169 +/- 24 (S.E.) mg/dl versus final 128 +/- 12 mg/dl; p less than 0.05]. In addition, the rate of total glucose production was significantly decreased after 30 days of hydrazine sulfate compared to placebo treatment (2.46 mg/kg/min versus 3.07 mg/kg/min, respectively; p less than 0.05). Toxic effects of hydrazine sulfate were minimal. Our results suggest that hydrazine sulfate can influence the abnormal carbohydrate metabolism associated with weight loss in patients with cancer.
Gross fetal body movements and fetal heart rate were studied serially during the last trimester of pregnancy by real-time ultrasound in 11 healthy women during the inhalation of 4% carbon dioxide in air. We observed that induction of maternal hypercapnia during the last 10 weeks of pregnancy had no effect on the percentage of time of gross fetal body movements or on fetal heart rate accelerations.
To determine whether maternal glucose administration can decrease the incidence of false positive nonstress tests, 296 nonstress tests were performed on 235 high-risk obstetric patients in a prospective controlled study. Patients were alternately given a 50 gm oral glucose drink or an equal volume of water 30 minutes prior to the commencement of each test. Among "fed" patients (last meal within 2 hour of the nonstress test) whether receiving glucose or water, and "fasted" patients who received glucose, there was no significant difference in the percentage of reactive tests at either 20 minutes (65.2%) or 40 minutes (87.3%) of testing. However, patients fasting and receiving water had a significantly decreased percentage of reactive tests, both at 20 minutes (48.3%, P less than 0.01) and at 40 minutes (76.7%, P less than 0.05). Glucose administered to fasted patients resulted in an increase in the incidence of reactive tests, although this was not statistically significant. Glucose administration had no effect on the nonstress test results when administered to fed patients.
This study demonstrated that fetal gross body movements were not significantly altered by fluctuations in maternal plasma glucose concentration. Fetuses moved episodically a relatively constant amount of time whether mother received water orally, 50 g of glucose orally or a 25 g bolus of glucose intravenously. In addition, depending on the length of the observational epoch, the incidence of fetal gross body movements differed. As the length of the observational period increased, the chance of finding no fetal gross body movements decreased and at intervals of 24 min duration, fetal gross body movements were absent in only 2% of 24 min periods examined, irrespective of whether they had received water orally, 50 g of glucose orally or 25 g of glucose intravenously. It is concluded that maternal carbohydrate intake was not an important determinant of fetal body movements in healthy fetuses at 32-34 weeks' gestation.
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Tracheal pressure and electrocortical activity were recorded in 10 unanesthetized fetal lambs in utero to determine the effect on fetal breathing movements (FBMs) of fasting and a subsequent infusion of glucose. The incidence of FBMs decreased significantly from 37.9% +/- 4.3% during fed control studies to 23.6% +/- 3.6% (P less than 0.05) after 24 to 36 hours of maternal fasting, with a related fall in fetal blood glucose. A 2-hour infusion of glucose to the fetuses of fasted animals resulted in a significant increase in FBMs to 39.5% +/- 4.9%, but only to a level similar to that in the fed control studies despite a twofold increase in the fetal concentration of glucose above fed control values. Changes in the incidence of FBMs paralleled the changes in fetal low-voltage electrocortical activity with alterations in glucose. In conclusion, FBM, although correlated with the concentration of glucose, may be influenced more by fetal hypoglycemia than hyperglycemia. Glucose appears to affect the incidence of FBM by altering the incidence of low-voltage electrocortical activity.
Continuous measurements of gross fetal body movements were made with an ultrasonic real-time scanner for periods of 24 hours in 31 women. Fetuses made 0 to 130 gross fetal body movements per hour which accounted for 0% to 50% of the time. At 38 to 39 weeks' gestational age, fetuses demonstrated a peak in activity between 2100 and 0100 hours. The longest period of complete absence of gross fetal body movements was 75 minutes. Maternal meals and glucose concentrations did not influence gross fetal body movements.
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