Orange County medics saved by 'super human' software.
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Efficiency, Organizational↗
Biomedical subjects
B Godfrey
Publications and source records attributed to B Godfrey.
Clinical distribution services. The big push.
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Centralized Hospital Services↗
Tracking beliefs and values. Leicester Royal Infirmary experience.
The turbulent environment in which NHS hospitals operate today necessitates a fundamental rethink of business principles. Not all organisations have a mission statement and although the benefits are controversial, it has become an increasingly important issue. An audit carried out at The Leicester Royal Infirmary provides a pointer as to how managers can gauge whether staff are familiar with the hospital's philosophy and how they feel about it. Brain Godfrey reports.
Attitude of Health Personnel↗
Macrophage-tropic strains of human immunodeficiency virus type 1 utilize the CD4 receptor.
To characterize the role of CD4 in human immunodeficiency virus type 1 (HIV-1) infection of macrophages, we examined the expression of CD4 by primary human monocyte-derived macrophages and studied the effect of recombinant soluble CD4 and anti-CD4 monoclonal antibodies on HIV-1 infection of these cells. Immunofluorescence and Western blot (immunoblot) studies demonstrated that both monocytes and macrophages display low levels of surface CD4, which is identical in mobility to CD4 in lymphocytes. Recombinant soluble CD4 and the anti-CD4 monoclonal antibody Leu3a blocked infection of macrophages by three different macrophage-tropic HIV isolates, and the cytopathic effects of HIV-1 infection were similarly prevented. Dose-response experiments using a prototype isolate which replicates in both macrophages and T lymphocytes showed that recombinant soluble CD4 inhibited infection of macrophages more efficiently than in lymphocytes. These results indicate that CD4 is the dominant entry pathway for HIV-1 infection of macrophages. In addition, recombinant soluble CD4 effectively blocks HIV-1 infection by a variety of macrophage-tropic strains and thus has the potential for therapeutic use in macrophage-dependent pathogenesis in HIV disease.
Antibodies, Monoclonal↗
Infection of monocyte-derived macrophages with human immunodeficiency virus type 1 (HIV-1). Monocyte-tropic and lymphocyte-tropic strains of HIV-1 show distinctive patterns of replication in a panel of cell types.
To characterize the host range of different strains of HIV-1, we have used four types of cells, primary monocyte-derived macrophages (MDM), primary PBL, a promonocyte cell line (U937), and a CD4+ T cell line (SUP-T1). These cells were infected with three prototype strains of HIV-1, a putative lymphocyte-tropic strain (IIIB), and two putative monocyte-tropic strains (SF162 and DV). Infections were monitored by assays for infectious virus, for cell-free and cell-associated viral antigen (p24), and for the proportion of cells infected by immunohistochemical staining. It was concluded that: (a) the use of four different cell types provides a useful biological matrix for distinguishing the tropism of different strains of HIV-1; this matrix yields more information than the infection of any single cell type. (b) A monocyte-tropic strain of HIV-1, such as strain SF162, shows a reciprocal host range when compared with a lymphocyte-tropic strain such as IIIB; strain SF162 replicates well in primary MDM but not in U937 or SUP-T1 cells, while strain IIIB replicates well in both U937 and SUP-T1 cells but not in MDM. (c) Both lymphocyte-tropic and monocyte-tropic strains of HIV-1 replicate well in PBL. (d) The promonocyte cell line, U937, and the T cell line, SUP-T1, differ markedly from primary cells, such as MDM and PBL, in their ability to support the replication of different strains of HIV-1; these cell lines cannot be used as surrogates for primary cells in host range studies of HIV-1 strains.
Antibodies, Monoclonal↗
Time of ovulation in the South Australian Merino ewe following synchronization of estrus. 1. Variation within and between flocks.
Observations were made by repeated laparoscopy to determine the time of ovulation in seven flocks of South Australian Merino ewes treated with pregnant mare serum gonadotropin (PMSG, 400 IU per ewe) and an intravaginal pessary containing 60 mg medroxy-progesterone acetate (MAP). Ovulation most often commenced within 57 h of pessary removal and was completed in all flocks within 81 h. There was, however, significant variation in the time of onset of ovulation; it did not commence until 69 h in one of three observations of Flock 1 and in two of three observations of Flock 2. On the other hand, in a flock of two-year-old nulliparous ewes (Flock 7), ovulation commenced significantly (P < 0.001) earlier than in most observations of other flocks, with 18 39 ewes ovulating within 57 h of pessary removal. The effect of the progestagen (MAP vs flugestone acetate) and the gonadotropin preparation (Pregnecol vs Folligon) on the time of ovulation were observed in separate studies. The characteristic time of ovulation was not influenced in either comparison. However, ovulation occurred significantly (P < 0.001) earlier in ewes treated with progesterone released from a controlled internal drug release dispenser (CIDR). The implications of these findings to artificial insemination and embryo transfer are discussed.
Journal Article↗
Heterogeneity of motilin immunoreactivity in mammalian tissue.
Motilin is a 22 amino acid peptide first isolated and sequenced from porcine gut. The use of antisera directed to the synthetic porcine gut motilin sequence has produced conflicting results as to regional distribution and histological localization of motilin in mammalian brain and gut. Motilin immunoreactivity has been detected (by RIA) in brain regions where no immunostaining is discernible. Variations in the patterns of staining are also observed with different antisera. These discrepancies have been explained by postulating species-, tissue-, and region-specific variations in peptide immunoreactivity, and variable cross reactivities of the independent antisera with these forms. The use of cloned porcine cDNA encoding gut prepromotilin in Northern blot analysis of brain regions expressing motilin-like immunoreactivity has also failed to reveal a homologous message, questioning the true nature of the immunoreactive material in the brain. Physiological studies, however, have suggested central roles for motilin in a variety of CNS (feeding behavior, bladder control, cerebral and brain stem modulation, pituitary growth hormone release) and gastrointestinal (gastric emptying, intestinal motility) functions. The motilin immunoreactive material detected in brain may be encoded by a distinct non-homologous gene, and still share amino acid homologies with the motilin sequence. Molecular biological characterization of the cell systems which contain motilin and motilin-like immunoreactivity should allow a better definition of their roles in these tissues.
Adrenal Medulla↗
Characterization of complementary deoxyribonucleic acid for precursor of porcine motilin.
Cloned cDNAs encoding the precursor protein for motilin and a novel peptide, motilin-associated peptide, were isolated from a library derived from porcine intestinal mucosa mRNA. Nucleotide sequence analysis predicts a precursor protein of 119 amino acids including a signal peptide in direct linkage with the 22 amino acid sequence for motilin, and a 70 amino acid peptide of unknown function. The putative bioactive moieties are separated by Lys-Lys, dibasic residues that serve as substrates for cleavage by proteolytic maturation enzymes in many polyprotein precursors. While there is an abundant literature detailing a spectrum of tissues and cell types which express motilin like immunoreactivity, analysis of mRNA derived from many of these tissues suggests that the mRNA for the mucosal motilin precursor is only transcribed in this tissue. The nature of the immunoreactive material in the central nervous system and other peripheral tissues remains to be determined.
Animals↗
Variation in the timing of multiple ovulations following gonadotropin releasing hormone treatment and its relevance to collecting pronuclear embryos of sheep.
Timing of superovulation was examined by repeated laparoscopy in two Merino flocks treated with either pregnant mare serum gonadotropin (PMSG) plus gonadotropin releasing hormone (GnRH) or follicle stimulating hormone (FSH) plus GnRH. Observations were made in May (late breeding season), August (early anoestrous season), November (late anoestrous season), and February (midbreeding season). Data examined were time to first ovulation, time to all ovulations, and time from first to last ovulation. A GnRH-induced synchrony in the timing of superovulation occurred in Flock 1 irrespective of the month of observation. Approximately 80% of ovulations were recorded within 3 h with the median ovulation occurring 47 to 49 h after progestagen treatment. A similar synchrony was observed in Flock 2 in November and February. However, in May and August, the timing was asynchronous with some ewes superovulating as early as 10 or more hours before the median time obtained in November and February. An examination of this phenomenon indicated that 1) it also occurred when GnRH was not included in the treatment protocol, 2) it occurred irrespective of when ewes were exposed to vasectomized rams, and 3) it was more common in anovular ewes induced to superovulate than in spontaneously cyclic ewes. We concluded that treatment protocols developed for the collection of pronuclear embryos in Merino ewes during the breeding season can be less reliable when used out of season, thus increasing the possibility of collecting two- to four-cell embryos.
Journal Article↗
Effect of eye movements on dynamic equilibrium.
The purpose of this study was to determine whether visual improvement of balance varies depending on the movement of the eye. Three movements were compared: static visual fixations, saccadic eye movements, and smooth pursuit eye movements. The subjects in this study were 35 healthy female volunteers. Balance was defined as the subjects' ability to maintain their equilibrium while keeping the unstable platform on which they stood within 5 degrees of the horizontal plane. The testing protocol consisted of five recorded practice trials, during which the subjects tried to maintain their balance without any visual instructions, and nine experimental trials, during which they tried to maintain their balance while visually following a videotaped target light projected onto a screen. The target light was sequenced randomly to remain stationary, move in a continuous horizontal path, or alternately jump between right and left. Data were analyzed using a one-way multivariate analysis of variance for repeated measures. A significant effect of vision on balance was found. The t tests for correlated samples revealed that time in balance during visual fixations and saccades was significantly longer than during tracking eye movements. We, therefore, concluded that tracking eye movements have a negative effect on balance. This information can be useful in treating patients with balance problems. For example, instructing patients to fixate visually on an object may aid their stability. Visual tracking of a moving limb, however, may impair a patient's stability.
Adolescent↗
Chromogranin A: the primary structure deduced from cDNA clones reveals the presence of pairs of basic amino acids.
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Amino Acid Sequence↗
On the origin of dehydroepiandrosterone sulphate in the blood of fetal sheep.
Total sulphoconjugated and unconjugated dehydroepiandrosterone (DHA) and total oestrone were measured in plasma of intact sheep fetuses, fetuses hypophysectomized at 104-112 days and fetuses bilaterally adrenalectomized at 98-101 days. At 120-127 days, the mean concentrations of total DHA and oestrone in intact fetuses (n = 13) were 29.7 +/- 4.2 (S.E.M.) nmol/l and 14.3 +/- 2.8 nmol/l respectively. At term, the values for total DHA and oestrone in hypophysectomized fetuses (n = 13) of 18.0 +/- 1.9 nmol/l and 9.1 +/- 2.0 nmol/l were significantly (P less than 0.05) lower than the intact group whereas in the adrenalectomized fetuses (n = 8) total DHA (80.8 +/- 13.0 nmol/l) was higher (P less than 0.05) and total oestrone values were similar to the intact animals. Intrafetal infusion of cortisol at term (1 mg/h for 84 h) raised levels of total oestrone in intact (n = 6; 12.3 +/- 2.9 vs 31.6 +/- 8.5 nmol/l) and adrenalectomized (n = 4; 14.2 +/- 2.6 vs 190.6 +/- 53.0 nmol/l) fetuses and of total DHA in hypophysectomized fetuses (n = 7; 16.0 +/- 1.9 vs 31.6 +/- 8.5 nmol/l) while infusion of ACTH (1-24) (5 micrograms/h) was without significant effect in any group. It is concluded that the ovine fetal adrenal in late pregnancy makes no significant contribution either to the high circulating concentrations of DHA sulphate or to the substrates for placental oestrogen synthesis.
Adrenal Glands↗
Estimation of fertility and fecundity in women receiving artificial insemination by donor semen and in normal fertile women.
The pregnancy rates after artificial insemination by donor semen (AID) have been compared with pregnancy rates in normal fertile women to assess the efficiency of AID. To do this, the curve y = a(1-(1-b)x) was fitted to life-tabled cumulative pregnancy rates. The equation describes a model in which the parameter a is the proportion of women who are potentially fertile under the conditions of treatment, and in which the parameter b is the pregnancy rate per cycle (or fecundity) of these fertile women. For 259 AID patients with no previous pregnancy a was 65% while for 57 AID patients with a previous pregnancy after AID 'a' was 99.9%. The values of b were similar for the two groups of patients, being 20% and 22% respectively. Women without fertility problems who had become pregnant after discontinuing oral contraception provided the reference group. Since only pregnant women were selected, a was 100% by definition. The values of b for the reference group were 22% for 100 primigravid women and 20% for 100 multigravid women. Only 65% of the AID patients were potentially fertile with AID, but those that were fertile became pregnant at the same rate as normal women who discontinued oral contraception.
Adult↗
Endocrinology of ovarian stimulation for in vitro fertilization.
Understanding of the endocrinology of in vitro fertilization has advanced rapidly in the past 5 years. Despite a multitude of ovarian stimulation regimens a particular regimen has not demonstrated a marked superiority. In principle the achievement of high FSH levels during the early follicular phase to recruit a maximum number of follicles with a tolerable degree of asynchrony for final maturation is confined to a limited time span or 'FSH window' of about 3 to 4 days before negative E2 feedback induces below-threshold FSH levels, thereby condemning all subsequent follicles in that cycle to atresia. It appears that one can widen and/or amplify the 'FSH window' too far from gross hyperstimulation resulting in the recruitment of many follicles with an intolerable degree of asynchrony. This may lead to a defective endocrine environment for the oocytes contained within these follicles or an abnormal luteal environment and an increased frequency of fertilization, cleavage and implantation failure. Whichever regimen is used, the stimulation should ideally be sufficient to promote the development of at least 3 follicles beyond 18mm diameter at the time of OPU. This can be expected to result in at least 2 embryos to be available for transfer. Monitoring of follicular response by a combination of E2 and ultrasonic parameters is recommended so that the administration of HCG is given close to the anticipated endogenous rise of LH. This can be achieved by detecting a reduction in the rate of E2 rise (to plateau).(ABSTRACT TRUNCATED AT 250 WORDS)
Chorionic Gonadotropin↗
Neonatal water metabolism: an objective postnatal index of intrauterine fetal growth.
The water metabolism of 103 newborn babies was determined over the first 10 postnatal days, by measuring water turnover rates by means of an isotope dilution technique. This technique involves the oral administration of the non-radioactive isotope of water, 2H2O, and the measurement of its urinary excretion by infrared spectrophotometry. The slope of the excretion curve after equilibration with the infant's body water was mathematically expressed as the rate constant. Using multiple obstetric and paediatric criteria, the babies were clinically classified into one of three categories, fully grown ("normal'), borderline or clearly growth retarded. The median values of the rate constants X 10(4) (h-1) for the three groups were 73.3, 85.9 and 100.2 and were highly significantly different from each other (P less than 0.0005) with no overlap of the 97% non-parametric confidence limits of each group. Neonatal water turnover increased with the clinical degree of intrauterine fetal growth retardation and within the limits of this study, this finding was unaffected by gestational age, birth weight or the neonatal environment. The results suggest that neonatal water metabolism is an objective postnatal index of fetal growth retardation.
Body Water↗
Patterns of progesterone, melatonin and prolactin secretion in ewes maintained in four different photoperiods.
Twenty-four-hour patterns of serum melatonin and prolactin levels were determined in ewes on nine occasions during a year. The sheep were maintained in four different photoperiods: room 1, simulated natural photoperiod; room 2, normal daylength extremes twice in 12 months, changes occurring in a regular fashion; room 3, alternating long (16 h) and short (8 h) days for 90 days; room 4, constant light. Cyclic ovarian activity, determined by twice-weekly determinations of serum progesterone, commenced in rooms 1, 2 and 3 after a transition from long to short daylength and terminated during long daylength. Thus in rooms 2 and 3 there were two periods of ovarian activity. In room 4 (constant light) ovarian activity began earlier than in room 1 and was of greater duration (240 days v. 190 days). Basal prolactin levels were highest (50-134 micrograms/l) during periods of long daylength and lowest (less than 10 micrograms/l) in short daylength. Ewes maintained in constant light had an intermediate level (21-62 micrograms/l) throughout the study. Melatonin secretion was lowest during daylight (less than 78 pmol/l) and highest during darkness. Night-time melatonin levels varied markedly from hour to hour and between individuals in rooms 1, 2 and 3. There was, however, no consistent seasonal change in the absolute levels of melatonin, although the duration of melatonin secretion did closely follow the length of the dark phase. There were no significant changes in melatonin levels during the oestrous cycle. Ewes kept in constant light had less than 78 pmol melatonin/l throughout the period of study. If the pineal gland is involved in transmitting photoperiodic information to the endocrine system, then it is most likely to be by means of an interaction between duration of melatonin secretion and an underlying change in sensitivity of end organs to melatonin.
Animals↗
The effect of clomid induced superovulation on human follicular and luteal function for extracorporeal fertilization and embryo transfer.
The administration of clomiphene citrate (Clomid) 150 mg/day from days 5-9 of the menstrual cycle to spontaneously ovulatory women in order to induce adequate multiple follicular development followed by timed laparoscopic aspiration of mature oocytes does not appear to impair luteal phase length or the steroid pattern of oestradiol-17 beta (E2) or progesterone (P) production as reflected by their peripheral blood concentrations. In Clomid stimulated cycles where preovular oocyte pickup (OPU) and embryo transfer (ET) occurred but no recognizable pregnancy resulted, the cycle length was 30.0 (s.e.m. = 0.3) days, the follicular phase length was 15.6 (s.e.m. = 0.3) days and the luteal phase length was 14.4 (s.e.m. = 0.3) days, which did not differ from a group of women having spontaneous ovular cycles. Following Clomid stimulation the dominant follicle was similar in size to the pre-ovulatory follicle in spontaneous uniovular cycles, but the second, third, fourth and fifth order follicles were significantly larger (P less than 0.0001). The ultimate test of luteal competence was the successful implantation of 11 concepti in 7 women (4 sets of twins) from 49 laparoscopies (14%) or 33 embryo transfers (21%). Comparisons between conceptual and non-conceptual embryo transfers following identical Clomid regimes showed no difference between plasma E2 concentrations at the time of hCG administration or the start of an endogenous LH rise; follicle volume, follicular fluid E2, P and testosterone concentrations were also not different. However, there was a trend for follicular P to be higher in the non-conceptual group indicating that advanced luteinization may hinder successful implantation. The follicular fluid androstenedione (A4) concentration was significantly lower in the conceptual group and the total androgen concentration (A4 + T) was also lower which was indicative of active aromatase activity in these follicles. It was concluded from this study that there was no indication to give exogenous hormonal support to the luteal phase, provided there was both optimal follicular growth and steroidogenic function following Clomid stimulation and that exogenous hCG was administered very close to the expected rise of LH. This observation was supported by the finding that timing of OPU based on a knowledge of the start of the LH surge was associated with a higher pregnancy rate than when hCG was administered and indicates that the endogenous mid-cycle events may permit superior maturation of the oocyte and/or permit better synchronization of endometrial maturation for implantation.
Adult↗
Sex ratio of birth resulting from artificial insemination.
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Australia↗