The role of histone acetylation in the allelic expression of the imprinted human insulin-like growth factor II gene

This study examines the relationship between the first cycle of in-vitro fertilization (IVF) and subsequent cycles. The results of all IVF cycles conducted at The Hammersmith Hospital or The Royal Masonic Hospital between 1988 and 1995 were studied including those cycles where egg recovery was abandoned due to poor ovarian response. All patients underwent a standardized treatment protocol. Of those women who achieved a clinical pregnancy during their first IVF attempt, 33% achieved a pregnancy during their second cycle, statistically significantly different from the 24% of patients conceiving during a second cycle who had failed to conceive during their first. 36% of those who achieved a biochemical pregnancy in their first cycle became pregnant in their second. Age was an important factor in the success of IVF treatment, with pregnancy rates of 48% in the 20-25 year age group falling to 8% in those aged > or =41 years. Cumulative pregnancy rates were 26% after one cycle, increasing to 43% after two cycles and reached 80% after seven cycles. A previous pregnancy significantly improved a couple's probability of conception in a later IVF cycle. Overall pregnancy rates per cycle were constant for the first three attempts. Cumulative pregnancy rates continued to rise to 72% after six cycles. Thus the more cycles a couple undergo (up to six) the greater their chance of a pregnancy.     

Neuropeptides in the insect brain: a review

Thirty-seven plants are listed, which are used by traditional healers in the central and southern parts of Somalia. For each species are listed: the botanical name with synonyms, collection number, vernacular name, medicinal use, preparation of remedy and dosage. Results of a literature survey are also reported including medicinal use, substances isolated and pharmacological effects. Three plants which should have been included in Part I of the series have been added and some corrections to that paper have been made. With these additions the series comprises 180 different plant species, distributed in 59 plant families.     

The importance of geriatrics to family medicine: a position paper by the Group on Geriatric Education of the Society of Teachers of Family Medicine

The role of geriatrics and geriatricians in family medicine remains unsettled. Despite a rapidly aging population, a tremendous shortage now exists of faculty with interest and expertise in geriatrics. Relatively few family practice residents choose to enter geriatric fellowship programs, and federal funding for such programs has been reduced. Despite accreditation requirements, residency programs are not always able to provide the range of geriatric experiences needed to properly prepare graduates to provide care for the broad range of older patients. Medical students' exposure to geriatrics remains limited. The Group on Geriatric Education of the Society of Teachers of Family Medicine believes that family medicine faculty must recognize and be committed to the notion that geriatrics is integral to family medicine. Both undergraduate and residency training programs should emphasize experience with geriatric patients in multiple settings. In particular, the nursing home should not be the main focus of geriatric training. The small number of certified geriatric faculty will be able to provide leadership, but a broad range of faculty must become involved in teaching geriatrics. Faculty development activities and continuing education programs to foster the necessary expertise will be essential to the accomplishment of this task.     

2-Hydroxypropyl-beta-cyclodextrin enhances phorbol ester effects on glucose transport and/or protein kinase C-beta translocation to the plasma membrane in rat adipocytes and soleus muscles

In rat adipocytes and soleus muscles, 2-hydroxypropyl-beta-cyclodextrin (CD) was found to have a relatively small or no effect on basal or insulin-stimulated hexose uptake, but markedly enhanced hexose uptake effects of phorbol esters and/or diacylglycerol. In rat adipocytes, the CD-induced enhancement of hexose uptake during concurrent phorbol ester treatment was not associated with an increase in GLUT4 glucose transporter translocation to the plasma membrane, which was stimulated comparably by insulin and phorbol esters. Moreover, CD appeared to activate or facilitate the activation of glucose transporters subsequent to their translocation to the plasma membrane during ongoing phorbol ester treatment. In rat adipocytes, CD also enhanced the translocation of protein kinase C (PKC)-beta to the plasma membrane during the action of phorbol esters, which alone had little or no effect on this specific PKC translocation. Although it is uncertain how CD alters the function of plasma membranes to enhance the translocation of PKC-beta to, and the activation of glucose transporters within, this subcellular fraction during phorbol ester treatment, our findings provide direct support for a two-step model in the activation of glucose transport. In addition, it seems clear that, at least in some cell types, simple phorbol ester treatment does not necessarily serve as a ubiquitous activator of all activable PKC pools and all potential PKC-mediated responses.     

Young children''s understanding of pretense expressions of independent agency

Data from the Cancer Registry of Slovenia were used in a cohort study to determine whether the incidence of second primary cancers in patients with first primary breast cancer differs from the incidence expected in the general population. Special interest was given to long-term survivors. The expected numbers of second primary cancers were calculated by multiplying the number of appropriate person-years at risk by the corresponding age- and calendar-period-specific cancer incidence rates for women in Slovenia. The risk of a second primary cancer was expressed as the standardized incidence ratio (SIR). Of the 8,917 patients newly diagnosed in the period 1961-85 and followed-up to the end of 1994, 547 (6.2 percent) developed second primary cancers, whereas 410 (4.7 percent) were expected (SIR = 1.3, 95 percent confidence interval [CI] = 1.2-1.4). The risk was higher among younger patients. In long-term survivors, the risk was increased significantly for second primary cancer of the breast (SIR = 1.4, CI = 1.1-1.7), lung cancer (SIR = 1.6, CI = 1.1-2.3), melanoma (SIR = 2.7, CI = 1.5-4.4) and non-melanoma skin cancers(SIR = 2.0, CI = 1.6-2.4), corpus uteri cancer(SIR = 1.6, CI = 1.2-2.1), ovarian cancer(SIR = 2.3, CI = 1.7-3.0), and thyroid cancer (SIR = 2.5, CI = 1.2-4.6). Our results confirm the findings of several cohort studies carried out in Europe, the United States, and Japan, indicating that breast cancer patients should be monitored carefully for the occurrence of second primary cancers.     

Pharmacodynamic modeling of the electroencephalographic effects of flumazenil in healthy volunteers sedated with midazolam

The purpose of this study was to model pharmacodynamically the reversal of midazolam sedation with flumazenil. Ten human volunteers underwent four different sessions. In session 1, individual midazolam pharmacokinetics and electroencephalographic pharmacodynamics were determined. In sessions 2 and 3, a computer-controlled infusion of midazolam with individual volunteer pharmacokinetic data was administered, targeting a plasma concentration corresponding to a light or deep level of sedation (20% or 80% of the maximal midazolam electroencephalographic effect) for a period of 210 minutes. After obtaining a stable electroencephalographic effect and constant midazolam plasma concentrations, a zero-order infusion of flumazenil was started until complete reversal of midazolam electroencephalographic effect was obtained. The flumazenil infusion was then stopped and the volunteer was allowed to resedate because of the constant midazolam drug effect. The electroencephalographic response was measured during a 180-minute period and analyzed by aperiodic analysis and fast-Fourier transforms. In session 4, a midazolam plasma concentration corresponding to a deep level of sedation was targeted for 210 minutes to examine for the possible development of acute tolerance. No flumazenil was given in session 4. For a light sedation level, with a mean midazolam plasma concentration of 160 +/- 64 ng/ml, the mean half-life of the equilibration rate constant of flumazenil reversal is 5.0 +/- 2.5 minutes, and the mean effect site concentration causing 50% of Emax is 13.7 +/- 5.8 ng/ml. For a deep level of sedation, with a mean midazolam plasma concentration of 551 +/- 196 ng/ml, the mean half-life of the equilibration rate constant is 3.9 +/- 1.5 minutes, and the mean effect site concentration causing 50% of Emax is 20.6 +/- 6.8 ng/ml. This study provides an estimate of the magnitude of the blood/central nervous system equilibration delay for flumazenil antagonism of midazolam sedation and further defines the usefulness of the electroencephalogram as a measure of midazolam pharmacodynamic effect.