Preoperative clear fluid fasting and endoscopy-measured gastric fluid volume in children.

BACKGROUND: In light of new recommendations to shorten clear fluid fasting time before anesthesia, our study aimed at exploring residual fluid volume in the stomach after different fasting times. We intended to perform direct endoscopic aspiration of stomach contents under vision, as part of routine gastroscopy assessment. Hereby we would be able to quantify true residual gastric fluid volume and acidity in children and measure their correlation with fasting times. METHODS: The study was performed as a single-center, prospective study in pediatric perioperative day care at a university-affiliated tertiary care center. Aspiration of gastric fluid contents was performed in anesthetized children aged 1-18 years undergoing an elective gastroscopy. Recorded data included patient fast time, last meal content, last clear fluid content, and aspirated gastric volume and pH, as well as patient characteristics. RESULTS: We included 253 gastroscopies, performed in 245 children. Mean fasting time for clear fluids was 6.9 h (range 1 h 40 min - 18 h 35 min) (SD 4.5). Mean age was 9.8 years (SD 5.1) and mean body weight was 33.2 kg (SD 18.7). Mean residual gastric volume was 12 mL (0-90) (SD 13.5) or 0.34 mL/kg (SD 0.37) and mean pH was 1.5 (SD 0.9). No significant correlation was observed between clear fluid fasting time and the child's residual gastric fluid volume per kg body weight (r = -.103, p = .1), nor between clear fluid fasting time and the pH of the residual gastric fluid (r = -.07, p = .3). In more than half of the patients the residual gastric volume was less than 10 mL, unrelated to fasting time. CONCLUSIONS: In children undergoing gastroscopy, we could not demonstrate any association between clear fluid fasting time and the child's residual gastric fluid volume per kg body weight. Since we did not see a clinically relevant association between clear fluids fasting time and gastric residual volume, this study may support the recommendation to shorten clear fluids fasting time.

Cervical dilation at the time of epidural catheter insertion is not associated with the degree of prolongation of the first or second stages of labor, or the rate of instrumental vaginal delivery.

INTRODUCTION: Epidural analgesia (EA) is an established option for efficient intrapartum analgesia. Meta-analyses have shown that EA differentially affects the first stage of labor but prolongs the second. The question of EA timing remains open. We aimed to investigate whether EA prolongs delivery in total and whether the EA administration timing vis-à-vis cervical dilation at catheter insertion is associated with a modulation of its effects on the duration of the first and second stages, as well as the rate of instrumental vaginal delivery in primiparas and multiparas. MATERIAL AND METHODS: A retrospective electronic medical records-based study of 18 870 singleton term deliveries occurring in our institution from 2003 to 2015. Cervical dilation was determined within a half-hour of EA administration. We examined whether cervical dilation at EA administration correlated with the duration of the first and/or second stage, with the rate of prolonged second stage, and with the rate of interventional delivery. The study group was stratified to 10 subgroups defined by 1-cm intervals of cervical dilation at EA administration. Logistic regression modeling was applied to analyze the association between EA timing and rate of instrumental delivery while controlling for possible confounders. RESULTS: In primiparas, receiving EA correlated with longer medians of active first stage (+51 minutes; P < .001) and second stage (+55 minutes; P < .001). In multiparas, median increases in active first stage (+43 minutes; P < .001) and second stage (+8 minutes; P < .001) were noted. The timing of EA, vis-à-vis cervical dilation (1-10 cm) was not associated with a substantial modulation of these effects. Logistic regression showed that cervical dilation at EA was not associated with a higher instrumental vaginal delivery rate. CONCLUSIONS: Epidural analgesia prolonged the first and second stages of labor vs no epidural. Having EA was associated with a higher instrumental delivery rate but not with higher rates of maternal or neonatal complications, in primi- and multiparas. Importantly, the timing of EA, vis-à-vis cervical dilation, was not associated with substantial changes in the duration of labor stages or the instrumental delivery rate. Thus, EA may be offered early in the first stage of labor.

[ABDOMINAL WALL BLOCKS FOR POST CESAREAN DELIVERY ANALGESIA].

INTRODUCTION: Intrathecal morphine administration at the time of neuraxial anesthesia performance is the gold standard for post-cesarean delivery (CD) analgesia. When intrathecal morphine administration is inappropriate or contraindicated, the use of systemic analgesic options increase side effects and risks to both the parturient and the breastfeeding neonate. Moreover, systemic analgesia is often inadequate. The increased clinical use of ultrasound has made way for regional analgesia techniques, mostly in the form of local anesthesia injected between muscular planes. The transversus abdominis plane (TAP) block is the most well-known and the most commonly used for Cesarean delivery. It has been shown to be effective in the absence of intrathecal morphine administration. It has however, not been shown to be beneficial when intrathecal morphine has been administered. Other, newer techniques are being increasingly used and investigated. Some may prove to be superior to the TAP block. These techniques include: ilioinguinal/ilio-hypogastric nerve blocks (II-IH), the quadratus lumborum (QL) blocks and the erector spinae plane (ESP) block. In this review, we will discuss and assess these techniques regarding analgesia following CD.

Obstetric anesthesia services in Israel snapshot (OASIS) study: a 72 hour cross-sectional observational study of workforce supply and demand.

BACKGROUND: We planned an observational study to assess obstetric anesthesia services nationwide. We aimed to assess the effect of the anesthesia workload/workforce ratio on quality and safety outcomes of obstetric anesthesia care. METHODS: Observers prospectively collected data from labor units over 72 h (Wednesday, Thursday and Friday). Independent variables were workload (WL) and workforce (WF). WL was assessed by the Obstetric Anesthesia Activity Index (OAAI), which is the estimated time in a 24-h period spent on epidurals and all cesarean deliveries. Workforce (WF) was assessed by the number of anesthesiologists dedicated to the labor ward per week. Dependent variables were the time until anesthesiologist arrival for epidural (quality measure) and the occurrence of general anesthesia for urgent Cesarean section, CS, (safety measure). This census included vaginal deliveries and unscheduled (but not elective) CS. RESULTS: Data on 575 deliveries are from 12 maternity units only, primarily because a major hospital chain chose not to participate; eight other hospitals lacked institutional review board approval. The epidural response rate was 94.4%; 321 of 340 parturients who requested epidural analgesia (EA) received it. Of the 19 women who requested EA but gave birth without it, 14 (77%) were due to late arrival of the anesthesiologist. Median waiting times for anesthesiologist arrival ranged from 5 to 28 min. The OAAI varied from 4.6 to 25.1 and WF ranged from 0 to 2 per shift. Request rates for EA in hospitals serving predominantly orthodox Jewish communities and in peripheral hospitals were similar to those of the entire sample. More than a fifth (13/62; 21%) of the unscheduled CS received general anesthesia, and of these almost a quarter (3/13; 23%) were attributed to delayed anesthesiologist arrival. CONCLUSIONS: Inadequate WF allocations may impair quality and safety outcomes in obstetric anesthesia services. OAAI is a better predictor of WL than delivery numbers alone, especially concerning WF shortage. To assess the quality and safety of anesthetic services to labor units nationally, observational data on workforce, workload, and clinical outcomes should be collected prospectively in all labor units in Israel.

An Enantiomer of an Oral Small-Molecule TSH Receptor Agonist Exhibits Improved Pharmacologic Properties.

We are developing an orally available small-molecule, allosteric TSH receptor (TSHR) agonist for follow-up diagnostics of patients with thyroid cancer. The agonist C2 (NCGC00161870) that we have studied so far is a racemic mixture containing equal amounts of two enantiomers, E1 and E2. As enantiomers of many drugs exhibit different pharmacologic properties, we assessed the properties of E1 and E2. We separated the two enantiomers by chiral chromatography and determined E2 as the (S)-(+) isomer via crystal structure analysis. E1 and E2 were shown to bind differently to a homology model of the transmembrane domain of TSHR in which E2 was calculated to exhibit lower binding energy than E1 and was, therefore, predicted to be more potent than E1. In HEK293 cells expressing human TSHRs, C2, E1, and E2 were equally efficacious in stimulating cAMP production, but their potencies were different. E2 was more potent (EC50 = 18 nM) than C2 (EC50 = 46 nM), which was more potent than E1 (EC50 = 217 nM). In primary cultures of human thyrocytes, C2, E1, and E2 stimulated increases in thyroperoxidase mRNA of 92-, 55-, and 137-fold and in sodium-iodide symporter mRNA of 20-, 4-, and 121-fold above basal levels, respectively. In mice, C2 stimulated an increase in radioactive iodine uptake of 1.5-fold and E2 of 2.8-fold above basal level, whereas E1 did not have an effect. C2 stimulated an increase in serum T4 of 2.4-fold, E1 of 1.9-fold, and E2 of 5.6-fold above basal levels, and a 5-day oral dosing regimen of E2 increased serum T4 levels comparable to recombinant human TSH (rhTSH, Thyrogen(®)). Thus, E2 is more effective than either C2 or E1 in stimulating thyroid function and as efficacious as rhTSH in vivo. E2 represents the next step toward developing an oral drug for patients with thyroid cancer.

Responses to salinity of grapevine plants with split root systems.

Grape yield, shoot and root vigour and water use by grapevine plants with split root systems were investigated. Some plants had both root parts continuously irrigated either with fresh or with saline water. Some plants got a dual treatment; one portion got fresh water and the other saline water. The irrigation water of a third group was changed during the experiment from fresh to saline water or vice versa. Fruit yield and root and shoot viability were positively correlated with the actual water use. Water ascent along the stem of the grapevines was found to be sectorial. Most of the water was supplied by the freshwater roots. Only small quantities of water were supplied by salt-affected roots to their respective twigs. Changes in the water quality of the root medium induced a dual effect: (a) a fast response, caused by the direct change in the ambient w7 ater potential; and (b) a long-term response that developed over several weeks. The latter response was induced by the development of new roots, or by death of others, upon a change in the quality of the irrigation water. The commonly used grapevine plants of the Arava valley are negatively affected by NaCl already at concentrations below 100 mM. Under such conditions, shoot growth and fruit yield were seriously inhibited, even when one part only of the root system was exposed to saline water.

Calcium-dependent actions of gonadotropin-releasing hormone agonist and luteinizing hormone upon cyclic AMP and progesterone production in rat ovarian granulosa cells.

The Ca2+ dependency of the direct stimulatory effect of the gonadotropin-releasing hormone (GnRH) agonist analog [D-Ser(t-Bu)6]des-Gly10-GnRH-N-ethylamide (GnRHa) on progesterone production was investigated and compared to that of luteinizing hormone (LH) in rat granulosa cells from preovulatory follicles. Removal of extracellular Ca2+ by EGTA, or the use of the Ca2+ channel blockers verapamil and La3+, resulted in complete inhibition of GnRHa-induced progesterone production and a partial inhibition of LH-stimulated progesterone production (80, 80 and 50% inhibition respectively for EGTA, verapamil and La3+). Removal of extracellular Ca2+ increased the ED50 for LH-induced cAMP production by four-fold (from 80 to 330 ng/ml) and decreased maximal nucleotide formation by 44%. LH-induced cAMP production was also inhibited partially by verapamil (35%) at 10(-4) M drug concentration. GnRHa had no effect on cAMP production in the presence or absence of Ca2+. GnRHa and LH were found to have maximal effects on progesterone production at about 0.5 mM of Ca2+ in the incubation medium. On the other hand the stimulatory effect of dibutyryl cAMP [Bu)2cAMP) on progesterone production showed little dependency on extracellular Ca2+. The calmodulin antagonist trifluoperazine (TFP) caused concentration-dependent inhibition of the stimulatory action of GnRHa and LH on progesterone production with IC50 values of 3 and 8 microM, respectively. The stimulatory effect of (Bu)2cAMP on progesterone synthesis was attenuated by verapamil and TFP. These results indicate that the direct stimulatory effect of GnRH on ovarian progesterone production is absolutely dependent on Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of ovulation in amenorrheic patients with gonadotropin-releasing hormone and human menopausal gonadotropin.

In five hypothalamic amenorrhea patients who underwent chronic intermittent gonadotropin-releasing hormone (GnRH) therapy for induction of ovulation, small doses (2 to 4 ampules/day) of human menopausal gonadotropin (hMG) were administered 9 to 32 days after the start of GnRH treatment. In seven treatment cycles, the addition of hMG initiated a sudden rise of 17 beta-estradiol concentrations, followed by a luteinizing hormone and follicle-stimulating hormone surge and ultrasonographic evidences of ovulation. Four of five patients conceived (singleton pregnancies) after the first or second treatment course. There were no clinical signs of ovarian hyperstimulation. Combined therapy of GnRH and hMG may be useful, therefore, for the treatment of hypothalamic amenorrhea patients who demonstrate prolonged follicular phases or luteinized unruptured follicle syndrome under chronic treatment with pulsatile GnRH alone.

Pulsatile luteinizing hormone-releasing hormone therapy in women with polycystic ovary syndrome.

Induction of ovulation with pulsatile luteinizing hormone-releasing hormone (LH-RH) therapy was attempted in 48 women with polycystic ovary disease (PCOD) and clomiphene citrate (CC) resistant anovulation. Fourteen women ovulated regularly, 23 ovulated variably, but 11 did not ovulate at all. Fifty-two of the 108 cycles of pulsatile LH-RH therapy alone (15 mu gm per pulse, one pulse every 90 minutes) administered through the subcutaneous route were ovulatory. In patients who did not ovulate on subcutaneous LH-RH, treatment with CC (100 mg per day for 5 days) was added to the LH-RH therapy in an additional 33 cycles, of which 21 were ovulatory. In those who did not respond to the combination of treatments, the same dose of LH-RH was administered intravenously: 14 of 29 cycles of intravenous therapy were ovulatory. The overall cumulative conception rate after 6 months of therapy was 60%. When recalculated for ovulatory cycles alone it was 90%, indicating that failure of ovulation was the only cause of the failure of conception. Analysis of the clinical and endocrine findings indicated that failure to ovulate was associated with obesity and hyperandrogenization. Ten of the 23 conceptions ended in miscarriage, 8 within 4 weeks of ovulation. The authors conclude that infertility in patients with PCOD is not optimally corrected by pulsatile LH-RH therapy.

Calcium homeostasis, bone metabolism and safety aspects during long-term treatment with a GnRH agonist.

Thirty-five women with symptomatic fibroids were treated with monthly injections of 3.2 mg microcapsulated D-Trp-6-LHRH for 6 months. During treatment serum 17 beta-oestradiol levels decreased, falling to castration levels associated with a reduction in the volume of the fibroids. In 16 patients a complete calcium homeostasis and bone metabolism work-up was carried out during treatment and subsequently for a 6-month follow-up period. Bone mineral content (BMC) and Compton bone densitometry readings remained unchanged. There were significant increases in serum calcium phosphate and alkaline phosphatase concentrations. A slight although not significant increase was observed in osteocalcin and parathyroid hormone (PTH) serum levels. Serum 1,25(OH)2D3 values decreased significantly after 3 months of treatment. Urinary hydroxyproline/creatinine and calcium/creatinine ratios as well as 24-h urinary calcium values increased significantly during the treatment period but decreased rapidly to pretreatment values after 3 months in the follow-up period. The endocrine changes induced by the GnRH-agonist treatment were associated with reversible biochemical signs of increased bone turnover and no significant changes in bone mass, suggesting that the treatment can be administered safely for a period of 6 months in patients with oestrogen-dependent diseases.

Physiological Aspects Related to Tolerance of Spring Wheat Cultivars to Septoria tritici Blotch.

ABSTRACT The susceptible wheat cultivar Miriam exhibited tolerance under severe infection of Septoria tritici blotch (STB). Nethouse and greenhouse trials confirmed former field results in which losses in grain weight of 'Miriam' wheat due to STB infection were significantly lower than those of the susceptible cultivar Barkai, under equivalent severity and the same disease progress curve. Several physiological mechanisms that may explain this tolerance of 'Miriam' wheat were studied. A comparison between protected and infected plants proved that carbohydrate reserves in the culms and other vegetative plant parts did not account for the lower losses in grain weight of 'Miriam'. Each tiller was shown to be independent in its supply of carbohydrates to its grains, and no import from secondary tillers was observed. Differences in the ratio between grain weight and vegetative biomass could not explain the sustained grain filling of infected plants of 'Miriam'. The daily balance of CO(2) exchange of the ears was negative, since carbon fixation by the spike in the light was more than counterbalanced by night time spike respiration. Radioisotope studies revealed that mature, infected 'Miriam' plants maintained as large a percentage of the carbohydrates fixed at the vegetative stage and early grain filling as healthy plants. On the other hand, under the same conditions, infected 'Barkai' plants lost a larger fraction of these carbohydrates. The rate of carbon fixation per unit of chlorophyll and per residual green leaf area of infected 'Miriam' was higher than in healthy plants. It is proposed that this enhancement of photosynthesis in residual green tissue of infected plants of the tolerant cultivar Miriam compensates for the loss of photosynthesizing tissue due to STB.

Effects of long-term treatment with bromocriptine on pituitary prolactinoma in a male.

Poor surgical results are obtained when operating on large prolactinomas, especially when an extrasellar growth is demonstrated. Several groups have reported tumor regression following bromocriptine treatment. A case report is presented of a young hyperprolactinemic man with a large pituitary adenoma with suprasellar extension, normal visual fields, decreased libido, impotence, hypogonadism and azoospermia. This man was treated with high doses of bromocriptine for a period of 5 months. A significant improvement of potency libido and sperm concentration associated with radiological evidence of a marked reduction of tumor size was noted following suppressive treatment with this ergot alkaloid.

Photosynthesis, chlorophyll integrity, and spectral reflectance in lichens exposed to air pollution.

The major objective of the present study was to identify the relationship of physiologial parameters of the photosynthetic system with the elemental content of the lichen Ramalina lacera (With.) J.R. Laund. Thalli of R. lacera were collected in an unpolluted site and transplanted in a national park and an industrial region in Israel for 8 mo. Analyses of photosynthetic activity, chlorophyll integrity, spectral reflectance, and amount of 11 metals were performed after this period of exposure. The normalized difference vegetation index (NDVI), indicative of the spectral reflectance response of the thallus, correlated with photosynthetic rate and chlorophyll and K content and correlated inversely with amounts of Ba, Cr, Cu, and Ni. The NDVI appears to enable the detection of early signs of pollutant-induced stress before changes in other physiological parameters become apparent. Elevated amounts of Cr, Cu, Fe, Mn, Ni, and Zn in lichens transplanted to an industrial area and the correlation of Mn and Ni, Mn and V, Ni and V, Fe and Mn, Fe and V, and Fe and Zn point for the greater part to metal processing in a steel smelter. Correlations of Cr and Ni, Cu and Ni, Zn and Cu, Cu and Mn, and Zn and Ni could be related to metal processing in the industrial area but indicate also vehicular activity as a possible originator.

Influence of serum luteinising hormone concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome.

Women with the polycystic ovary syndrome do not respond well to treatment with luteinising hormone releasing hormone. To determine whether this might be due to an underlying endocrine disturbance basal concentrations of luteinising hormone were measured in 54 infertile women treated with pulsatile luteinising hormone releasing hormone and concentrations at the time of maximum follicular growth were measured in 23 of the patients. Forty one patients ovulated. Forty one patients ovulated and 27 conceived, but nine pregnancies terminated within four weeks after ovulation. Basal luteinising hormone concentrations were significantly lower in those who conceived (12.4 (range 1.3-29.0) IU/l) than in those who did not (19.0 (3.5-50.0) IU/l) and in those whose pregnancy progressed (9.6 (1.3-29.0) IU/l) than in those with early loss of pregnancy (17.9 (7.0-29.0) IU/l). Concentrations at the time of maximum follicular growth were significantly lower in women who ovulated (9.4 (2.9-35.4) IU/l) than in those who did not (29.0 (7.0-50.0) IU/l) and in those who conceived (6.2 (2.9-8.5) IU/l) than in those who did not (17.9 (4.0-50.0) IU/l). These results indicate that high concentrations of luteinising hormone during the follicular phase in women with polycystic ovaries have a deleterious effect on rates of conception and may be a causal factor in early pregnancy loss.

One hundred pregnancies after treatment with pulsatile luteinising hormone releasing hormone to induce ovulation.

OBJECTIVE: To review treatment with pulsatile luteinising hormone releasing hormone in infertile women who do not ovulate and are resistant to clomiphene after 100 pregnancies achieved with this treatment. DESIGN: Retrospective analysis of 146 courses of treatment over 434 cycles. SETTING: Infertility clinic. PATIENTS: 118 Women whose failure to ovulate was due to idiopathic hypogonadotrophic hypogonadism (n = 39), amenorrhoea related to low weight (n = 17), organic pituitary disease (n = 15), or polycystic ovaries (n = 47). INTERVENTIONS: Dose of 15 micrograms luteinising hormone releasing hormone/pulse subcutaneously every 90 minutes given with a miniaturised pump throughout cycle monitored by ultrasound. Women with hypogonadotrophic hypogonadism had 48 courses, women with amenorrhoea related to low weight 23, women with organic pituitary disease 18, and women with polycystic ovaries 57. END POINT: Follow up of 100 pregnancies achieved in 77 women during six years after introducing treatment. MEASUREMENTS and main results--One hundred pregnancies (seven multiple, 28 miscarriages). Cumulative rates of pregnancy were 93-100% at six months in women with idiopathic hypogonadotrophic hypogonadism, amenorrhoea related to low weight, and organic pituitary disease. In women with polycystic ovaries (cumulative rate of pregnancy 74%) adverse prognostic factors were obesity, hyperandrogenism, and high luteinising hormone concentrations, which were also associated with a high rate of early pregnancy loss. CONCLUSIONS: Treatment with pulsatile luteinising hormone releasing hormone is safe, simple, and effective, and the preferred method of inducing ovulation in appropriately selected patients. Compared with exogenous gonadotrophin treatment there is little need for monitoring, no danger of hyperstimulation, and a low rate of multiple pregnancies.

A selective TSH receptor antagonist inhibits stimulation of thyroid function in female mice.

Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of cAMP production stimulated by TSH, LH, or FSH. We tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 µM for TSHR and greater than 30 µM for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. In conclusion, we developed a selective TSHR antagonist that is effective in vivo in mice. This is the first report of a small-molecule TSHR antagonist active in vivo and may lead to a drug to treat Graves' disease.