Cardiopulmonary effects of nalbuphine hydrochloride and butorphanol tartrate in sheep

The cardiopulmonary, sedative and analgesic effects of butorphanol tartrate and nalbuphine hydrochloride were evaluated in six adult crossbred Dorset sheep (Ovis aries). The animals were divided randomly into two groups of three. The first group received butorphanol tartrate (0.5mg/Kg s.c.) followed in 3 days by nalbuphine hydrochloride (1 mg/Kg, s.c.). The second group received nalbuphine followed in 3 days by butorphanol. Cardiopulmonary parameters were evaluated at baseline (once the animal had accommodated to restraint); immediately following analgesic administration; and at 15, 30, 60, 90 and 120 minutes after analgesic administration. No significant changes (alpha greater than .05) from baseline were seen in any of the measured cardiopulmonary parameters from either the butorphanol or nalbuphine groups. Butorphanol produced the most dramatic analgesic and sedative effects with onset of both within 15 minutes of administration and peak effects occurring 30 minutes post injection. The degree of analgesia was diminished at 120 minutes while the sedative effect returned to near baseline by 90 minutes. The nalbuphine group also showed an onset of analgesia 15 minutes post injection reaching a peak effect after 30 minutes. However, onset of sedation occurred 30 minutes post injection achieving a peak effect at 60 minutes which was markedly less than that of butorphanol. As in the butorphanol group, analgesia was diminished at 120 minutes.     

Paracervical Block Anesthesia in Labour

The efficacy and safety of paracervical block anesthesia were studied in 153 patients in the first stage of labour. Transient decrease in uterine activity was noted in 77 patients. There was no acceleration in cervical dilatation following the block. The duration of action of the block in 80 primiparas was 31 to 120 minutes in 69, and over 120 minutes in five. In the 73 multiparas, 53 of the blocks lasted 31 to 90 minutes, eight from 90 to 120 minutes, and two over 120 minutes. The results were good in 66 primiparas and 54 multiparas. The blocks failed in four primiparas and six multiparas. Twenty-six infants had low Apgar scores, but in none could this be related to the paracervical block. There were no significant fetal or maternal complications.     

Time delays in provision of thrombolytic treatment in six district hospitals. Joint Audit Committee of the British Cardiac Society and a Cardiology Committee of Royal College of Physicians of London.

OBJECTIVE--To measure the delays between onset of symptoms and admission to hospital and provision of thrombolysis in patients with possible acute myocardial infarction. DESIGN--Observational study of patients admitted with suspected myocardial infarction during six months. SETTING--Six district general hospitals in Britain. SUBJECTS--1934 patients admitted with suspected myocardial infarction. MAIN OUTCOME MEASURES--Route of admission to hospital and time to admission and thrombolysis. RESULTS--Patients who made emergency calls did so sooner after onset of symptoms than those who called their doctor (median time 40 (95% confidence interval 30 to 52) minutes v 70 (60 to 90) minutes). General practitioners took a median of 20 (20 to 25) minutes to visit patients, rising to 30 (20 to 30) minutes during 0800-1200. The median time from call to arrival in hospital was 41 (38 to 47) minutes for patients who called an ambulance from home and 90 (90 to 94) minutes for those who contacted their doctor. The median time from arrival at hospital to thrombolysis was 80 (75 to 85) minutes for patients who were treated in the cardiac care unit and 31 (25 to 35) minutes for those treated in the accident and emergency department. CONCLUSION--The time from onset of symptoms to thrombolysis could be reduced substantially by more effective use of emergency services and faster provision of thrombolysis in accident and emergency departments.     

The turnover of cyclic AMP in cultured fibroblasts

The determination of the turnover of cAMP in WI-38 and VA13 cultured fibroblasts stimulated by prostaglandin E1 is reported. The method made use of data obtained from a process of continuously labeling the cellular adenine nucleotide pools by incubation with [3H]-adenine. The turnover of the cAMP was estimated from the delay in appearance of tritium label in the cAMP pool was compared to the cellular ATP. For WI-38 cells the half-life of cAMP when accumulation had reached a steady-state was 1.46 minutes; in the presence of 0.5 mM 1-methyl-3-isobutylxanthine (IBMX) the half-life was increased to 9.24 minutes. For VA13 transformed fibroblasts the half-life of cAMP determined by this method was 6.30 minutes. cAMP in these latter cells in the absence of hormone had a half-life of 3.01 minutes. This decrease supports the contention that the hormone has profound effects on phosphodiesterase as well as adenylate cyclase activities in these cells.     

Rapid Metabolic Changes in the Wounding Response of Leaf Discs following Excision

The dark respiration rate of discs from fully expanded tobacco leaves (Nicotiana tabacum) increased linearly with decreasing diameter, the relative increase being independent of leaf age. The wound respiration responsible for this situation reached a plateau within 15 minutes of excision. Metabolite analysis gave evidence for two independent effects, also unrelated to age. The first was a forward crossover between phosphoenolpyruvate and pyruvate which was found as early as 1 minute after excision and persisted for up to 40 minutes. It was attributed to activation of pyruvate kinase by a changed ionic balance resulting from membrane damage, was accompanied by a reverse crossover between triose phosphates and 3-phosphoglycerate, and was localized in the outer region of the discs. The second effect was a rapid rise in hexose monophosphate and ATP levels throughout the discs. After 1 to 10 minutes the ATP/ADP ratio rose strongly for at least 3 hours; after 20 to 40 minutes there was net synthesis of adenine nucleotide as ATP. These results indicate that extrapolation from leaf discs to intact leaves is highly inadvisable.     

Regulation of Mitosis in Living Cells. I. Mitosis under Controlled Conditions

A quantitative method has been devised to study mitosis in vitro by phase contrast and polarization microscopy. Mitosis in cell-wall-free endosperm cells of Haemanthus kathrinar Baker (the African blood lily) has been divided into 18 arbitrary stages or events. The time course for the various stapes, as well as the percentage of cells that proceed from one stage to another during a four hour observation period, are presented. Cells that were in prophase when selected for study proceeded from nuclear membrane breakdown to melaphase in 60 minutes and remained in melaphase for 30 minutes. Only 13 minutes was required to proceed from onset of anaphase to mid-anaphasc. Mid-anaphase provides a clear and precise baseline for determining the time required for succeeding stages to appear. The cell plate made its appearance 40 minutes after mid-anaphase and was completely formed 20 minutes later. The nuclear membranes also became evident at this latter time and nucleoli were visible 30 minutes later. Thus, the average time for a cell observed initially in prophase to proceed from nuclear membrane breakdown to formation of two daughter cells was just over three hours. A high percentage of cells that were in late prophase or later stages of mitosis at the time of initial observation completed mitosis during the observation period. The effect of the length of time a cell is subjected to experimental conditions upon its subsequent behaviour is assessed. These results form the basis for future studies of the effects of chemicals, particularly herbicides, upon cells in mitosis as observed in vitro by phase contrast and polarization microscopy.     

Application of new enhanced medium in indirect antiglobulin test by gel method

The objective of this study was to explore the efficacy of a new enhanced medium in indirect antiglobulin test by optimized gel method. Anti-IgG+ C3d and anti-IgG antiglobulin gel cards, and samples from three blood group systems: Rh, Kidd and MNSs were used. The new enhanced medium was incubated at 37°C for 5 minutes, low ionic strength solution (LISS) for 15 minutes, saline solution for 30 minutes, respectively. The sensitivity and specificity of blood group antibodies were then compared. The results showed that the specificity and sensitivity of the new enhanced medium incubated for 5 minutes were consistent with those of LISS and saline solution for 15 minutes and 30 minutes, respectively. The results suggest that the new enhanced medium be able to accelerate the binding of erythrocyte antibodies with antigens, reduce incubation time and optimize the detection process of indirect antiglobulin test by gel method.     

Early developmental processes in the fertilised honeybee (Apis mellifera) oocyte

The behaviour of sperm from egg penetration until creation of the zygote, the development of the maternal pronucleus, and the two first cleavage divisions were studied by use of fluorescence microscopy. It was found that 4-12 sperm penetrate the egg membranes prior to oviposition. Contrary to previous reports, we found that only 1-7 sperm move from their initial location just beneath the vitelline membrane and into the cytoplasm, where they develop into paternal pronuclei. At the time of oviposition, the oocyte nucleus was usually at the stage of metaphase I, rather than anaphase I as previously reported. At 26+/-2.5 minutes the meiotic process had entered the stage of metaphase II. The paternal and maternal pronuclei formed at 55+/-2.6 minutes, and they fused at 93+/-7.3 minutes. The mitotic division of the zygote was completed at 119+/-6.5 minutes.     

Heterolysosome formation in mouse liver

When formaldehyde-treated ¹³¹I-albumin was injected into mice, the total liver radioactivity did not change significantly from 5 minutes to 60 minutes after injection. There was a progressive increase with time in the amount of radioactivity associated with liver particles which could be released by osmotic shock; the quantity of material tightly bound to particles, but not releasable by osmotic shock, did not change. At five minutes after injection the liver particles did not release acid-soluble radioactivity into the medium when incubated at 37°. These particles contain the injected protein in osmotically releasable form not associated with proteolytic enzymes and therefore correspond to phagosomes. At 10, 30 or 60 minutes after injection, the particles degraded the protein at similar rates but the activity ceased after 90 minutes incubation when only 50 to 60% of the osmotically releasable material was hydrolyzed. This cessation of activity was shown to be due to a thermal disruption of the particles during incubation.     

Tissue and plasma levels of endothelin in free flaps

The goal of the study was to assess whether endothelin-1 levels are increased in tissue and plasma in free flaps. To assess this hypothesis, blood samples were taken from the general circulation before and after reperfusion and from the flap after reperfusion in 20 patients undergoing breast reconstruction with free transverse rectus abdominis musculocutaneous or deep inferior epigastric perforator flaps. Tissue samples were also taken from the flap before and after the period of ischemia. Peripheral blood samples of 10 ml each were taken before the vessels were clamped and at 10 minutes and 1 hour after the flap was recharged. The flap vein was catheterized with a smooth catheter to avoid endothelial trauma, and ischemic blood from the flap was obtained immediately after the artery was unclamped and 10 minutes later. Two skin samples of 2 cm each were taken: one after dissection of the flap before division of the vessels and one after reanastomosis of the veins (one or two veins). Statistical analyses were performed with the (nonparametric) Wilcoxon signed rank test. Flap ischemia time, from vessel division to the completion of the arterial anastomosis, ranged from 35 to 120 minutes (mean, 48 minutes). The plasma endothelin-1 level extracted from the flap was 4.34 +/- 0.85 pg/ml, significantly higher than baseline, 3.87 +/- 0.81 pg/ml (p < 0.0001). There was a small increase, 4.5 +/- 1.03 pg/ml (p = NS), 10 minutes after reperfusion. The peripheral level after venous anastomosis was 3.78 +/- 0.79 pg/ml, not significantly different from the peripheral plasma level, before the flap was raised. The peripheral plasma level 1 hour after reperfusion was 3.83 +/- 0.8 pg/ml, with no difference from baseline. The tissue level of endothelin-1 before clamping was 3.8 +/- 0.8 pg/mg and in postischemic tissue, 5.2 +/- 0.6 pg/mg, a statistically significant increase. The authors concluded that endothelin-1 levels are elevated in free flaps. This could be an explanation for vasospasm and may lead to therapy directed against the no-reflow phenomenon.     

Changes in the radioresistance of bacteria after the inhibition of proteosynthesis in the preirradiation phase

The strain ofEscherichia coli WP₂ (try_v) was irradiated with UV light, at a dosage of 240 erg/mm. Proteosynthesis was inhibited by the elimination of the essential amino acid from the cultivation medium. Changes in radioresistance were followed during 45 minutes of starvation and during the subsequent 45 minutes of restitution after the addition of the essential amino acid. The radioresistance of the cells showed a linear increase immediately after the removal of the essential amino acids, proportional to the duration of the inhibition of proteosynthesis. The increase in radioresistance was shown to be reversible. After the addition of the essential amino acid there was an immediate decrease in radioresistance which was most marked in the first 15 minutes.     

Second meiotic division and polar body formation in mouse eggs fertilized in vitro

The second meiotic division and polar body formation in mouse eggs fertilized in vitro were observed by phase-contrast and polarizing microscopy, and recorded by time-lapse cinematography. Eggs were collected from oviducts of mice that had been superovulated by injections of PMS and HCG. Some eggs, inseminated with spermatozoa that had been collected from caudae epididymides of mature male mice and cultured for two to three hours before insemination, were observed continuously on a glass slide under a phase microscope. Other eggs were inseminated in Petri dishes in a 5% CO₂ incubator and examined every 20 minutes for 180 minutes. Compatible results in both sets of eggs showed that formation of the second polar body began 25–40 minutes after fusion of spermatozoon with the vitellus; it was completed 40–60 minutes later; anaphase II lasted approximately five minutes before the appearance of the furrow abstricting the second polar body. It is suggested that the furrowing associated with second polar body formation is guided by the same kind of forces that divide a cell mitotically.     

In vivo electrochemical recording of acetaminophen in non human primate brain

In vivo electrochemical recordings were obtained from the caudate nucleus of three young adult pigtail monkeys (M. nemestrina) following the oral administration of acetaminophen (APAP) (75 mg/kg). Using linear sweep voltammetry, electrodes in the right and left caudate were scanned alternately every five minutes. The electrochemical peak resulting from the APAP was monitored for at least 140 minutes following drug administration. Maximum APAP levels were detected in the monkey caudate 40 minutes following drug administration. Both right and left caudate displayed an identical time course, with oxidation potentials (Eox) similar on both sides of the brain. Blood samples were collected from one monkey by means of an intravenous catheter. Samples were obtained at approximately 5-minute intervals and over a period of 140 minutes following oral administration of APAP. Concentration of APAP in serum peaked 25 minutes after administration. In this animal the maximum electrochemical peak height was detected 40 minutes following APAP administration. These findings demonstrate the ability to measure APAP in the caudate nucleus of awake monkeys by means of electrochemical detection. This method may be useful for calibrating electrochemical electrodes in vivo, and it also provides a model system for studying drug kinetics in the brain.     

In vivo 31P NMR in crustacean muscles: fatigue and recovery in the tail musculature from the prawn Palaemon elegans

31P NMR has been used to observe the in vivo phosphometabolite concentrations in the tail musculature from the prawn Palaemon elegans, at rest and after escape swimming and subsequent recovery. Muscular fatigue corresponds to a 60% breakdown of phosphoarginine, and a 45% increase of sugar phosphates. The pHi fell from 7.10 to 6.86. During recovery, the sugar phosphates and arginine phosphate are replenished after 20 minutes. The ATP concentration did not change throughout the experiment. The pHi was restored within 20 minutes.     

Duration of Last Attack in 998 Fatal Cases of Coronary Artery Disease and its Relation to Possible Cardiac Resuscitation

All the deaths attributed to coronary artery disease and occurring in Belfast during one year were studied.The frequency distributions of the cases by interval of time between onset of the last attack and death are given for those not admitted to hospital, for those admitted to hospital, and for those already in hospital for some other cause of illness.Sixty per cent. of all the deaths occurred outside hospital. This indicates that the problem of cardiac resuscitation in coronary artery disease is to a considerable extent an extra-hospital one.Twenty-seven per cent. of the men and 22% of the women died within 15 minutes, but the median period of survival was 3 hours 30 minutes for men and 6 hours 18 minutes for women.The median time interval from the onset of the attack to sending for medical aid was 1 hour 17 minutes for men and 1 hour 6 minutes for women, and from summoning medical aid to sending for the ambulance 59 minutes for men and 1 hour 26 minutes for women. Ninety-six per cent. of the ambulance journeys to the patient were accomplished in less than 20 minutes.It was found among men, but not among women, that the duration of survival tended to be longer in older patients and in second or subsequent attacks.Of the 596 who did not gain admission to hospital 229 (23% of all the 998 patients) were known to have survived for more than half an hour after the onset of the fatal attack; 182 (18%) survived for more than one hour; and 143 (14%) survived for more than two hours. It is among these that there would appear to be special scope for the cardiac ambulance, providing that medical aid is sought and the ambulance is summoned without delay.     

Study on the metabolism of lyso-platelet activating factor (lyso-PAF) in human paranasal sinus mucosa. The cultured ciliated epithelium can convert lyso-PAF to PAF

The conversion of lyso-platelet activating factor (lyso-PAF) to PAF in cultured paranasal sinus mucosa obtained from normal human subjects was studied. The PAF concentration in the medium was determined after addition of lyso-PAF. PAF became detectable at 10 minutes after the addition of 10⁻⁸M lyso-PAF, and reached a maximum concentration (3.25×10⁻⁹M) at 20 minutes. The PAF level then gradually declined to become undetectable at 60 minutes after addition of lyso-PAF. Thus PAF is very unstable having a half-life calculated to be 12.8 minutes with an elimination constant of k=0.05377 minutes⁻¹. In contrast, lyso-PAF is known to be a stable metabolite of PAF as well as a precursor of PAF. The results obtained from this study suggest that the turnover of lyso-PAF to PAF may play a role in evoking prolonged inflammation in target organs or tissues.     

Anesthesia in the mouse using a combination of ketamine and promazine

An anesthetic combination of ketamine and promazine was tested in 25 male and 25 female mice of each of two strains. The mean induction time was 5 minutes for the C57BL/6We mouse and 8 minutes for the DBA/2We mouse. No sex differences were observed. The mean duration time was 45 minutes for the C57BL/6We male, 53 minutes for the C57BL/TWe female, 29 minutes for the DBA/2We male, and 35 minutes for the DBA/2We female. The mean recovery time was 39 minutes for the C57BL/6We male, 38 minutes for the C57BL/6We female, 21 minutes for the DBA/2We male, and 24 minutes for the DBA/2We female. The drug combination provided effective anesthesia for these strains of the laboratory mouse for a period of 30--50 minutes after a single intramuscular injection.     

A comparison of fertilization envelope development in three species of Strongylocentrotus (S. franciscanus, S. droebachiensis, and S. purpuratus)

The ultrastructure of fertilization envelope (FE) development and the polypeptide spectra of Strongylocentrotus franciscanus and S. droebachiensis envelopes were compared to S. purpuratus. In S. franciscanus, the FE reached its maximum thickness of 67 nm by 3 minutes postinsemination (PI), and final structuralization was observed by 40 minutes PI. The fully formed FE did not have microvillar impressions (casts) and was symmetrical, with outer double laminar elements surrounding an amorphous central region. Isolated S. franciscanus FEs were soluble in reducing and denaturing solvents and the same set of 33 polypeptides ranging from 18.5 to 260 kD was detected in FEs isolated from 10 to 180 minutes PI. The S. droebachiensis FE retained microvillar casts, assumed its definitive form by 3 minutes PI, and was 70 nm thick between microvillar impressions. Isolated S. droebachiensis FEs were partially soluble in reducing and denaturing solvents, and the polypeptide spectra of FEs isolated between 10 and 60 minutes PI were identical and showed 14 polypeptides from 18.5 to 265 kD. Antisera against extracted FEs and the FE extract from S. purpuratus were immunologically cross-reactive (using an enzyme-linked immunosorbent assay) with S. franciscanus and S. droebachiensis FE preparations; immunoblots identified 13 and 5 cross-reactive polypeptides, respectively. Most of the cross-reactive polypeptides were of slightly different molecular weight. Based on comparative ultrastructural, solubility, and electrophoretic data, we suggest that S. droebachiensis FE development is most like that observed in S. purpuratus.     

Vasopressin and epinephrine stimulation of phosphatidylinositol breakdown in the plasma membrane of rat hepatocytes

Hepatocytes obtained from rats injected 18 hours previously with tritiated inositol showed significant phosphatidylinositol breakdown after treatment with 20 mU/ml vasopressin or 10 uM epinephrine. Vasopressin produced only a 4.7% and 7.4% decrease in breakdown of total phosphatidylinositol at 5 and 15 minutes. The subcellular localization of vasopressin and epinephrine induced phosphatidy linositol breakdown was examined in prelabeled hepatocytes incubated with 20 mU/ml vasopressin or 10 uM epinephrine for 5 minutes. There was an appreciable loss (16 to 19%) of labeled phosphatidylinositol from the plasma membrane of isolated hepatocytes exposed to epinephrine or vasopressin for 5 minutes. There was no significant breakdown of the labeled phosphatidylinositol present in endoplasmic reticulum. These results indicate that vasopressin and epinephrine stimulate phosphatidylinositol breakdown in the plasma membrane after activation of cell surface receptors.