Systematic review and network meta-analysis of hydrosalpinx treatment before in vitro fertilization.

OBJECTIVES: To compare different methods to treat hydrosalpinx, based on both ablative and non-ablative approaches, in infertile patients before undergoing IVF-ET. METHODS: Systematic review and network meta-analysis (NMA) of comparisons between different treatments of hydrosalpinx in infertile patients undergoing IVF. DATA SOURCES: structured searches in common citation databases. Study inclusion criteria: peer-reviewed randomized trials (RCT) or cohort studies comparing effects of salpingectomy, laparoscopic proximal tubal occlusion (LTO), insertion of intratubal device (ITD), sclerotherapy, ultrasound-guided aspiration and no treatment, on live birth, ongoing pregnancy, clinical pregnancy as main outcomes, considering also miscarriage, ectopic pregnancy and complications as secondary outcomes. Principal NMA included RCT, and aggregated NMA of RCT and observational studies was carried out. Pooled effects have been estimated by Odds Ratio (OR) and its 95% confidence interval (CI) for direct and indirect-mixed comparisons, derived from random-effects models. Imprecision and heterogeneity of NMA estimations was assessed by comparison of its 95% CI with predefined intervals for clinically relevant size of effect (OR <0.9 or >1.1). Surface under the cumulative ranking curve (SUCRA) were used to predict treatment rankings for each outcome. RESULTS: Nine RCT were included in main analysis, plus 17 additional observational studies in additional analysis. NMA of RCT did not identify significant differences in the effect of compared treatments on live birth rate, and LTO was the option with the highest value of SUCRA (0.92, mean rank: 1.2). Salpingectomy and US-aspiration associated to a significant increase of ongoing pregnancy rate compared to no treatment, according to NMA results (NMA OR: 4.35; 95% CI: 1.7, 11.14 and 2.8; 95% CI: 1.03, 7.58 respectively). Salpingectomy had the highest SUCRA value (0.88, mean rank: 1.4). NMA estimated significant increase of clinical pregnancy rate for salpingectomy compared with no treatment (NMA OR: 2.24; 95% CI: 1.3, 3.86) as well as for LTO versus no treatment (NMA OR: 2.55; 95% CI: 1.2, 5.41). Both comparisons were affected by a high grade of heterogeneity. For clinical pregnancy, LTO was the intervention with highest SUCRA (0.85; mean rank: 1.6). Regarding secondary outcomes, feasible NMA estimates did not support significant differences between treatments effects. According to aggregated NMA including randomized and observational studies, sclerotherapy showed significant beneficial effects on live birth rate compared to no treatment (NMA (OR: 4.6; 95% CI: 1.21, 17.46). Compared with untreated patients, the aggregated NMA estimates a higher ongoing pregnancy rate in patients treated with salpingectomy (NMA OR: 3.35; 95% CI: 2.12, 5.12), US-aspiration (NMA OR: 2.16; 95% CI: 1.28, 3.65) and LTO (NMA OR: 2.46; 95% CI: 1.11, 5.43). Salpingectomy and LTO produced a higher beneficial effect compared to ITD, based on both direct and indirect comparisons. Salpingectomy obtained the highest SUCRA value in rank of effects on ongoing pregnancy (0.94; mean rank: 1.2). NMA found significant effects on clinical pregnancy for comparisons between the different active management procedures compared with no treatments, with the exception of ITD insertion. LTO had more increasing effect on clinical pregnancy rate compared with US-aspiration (NMA OR: 2.04; 95% CI: 1.05, 3.97), while for the rest of the comparisons between procedures no significant differences were identified. NMA ranked LTO as the treatment with a highest SUCRA value (0.91; mean rank: 1.5). NMA prediction models identified LTO as best intervention to reduce miscarriage (SUCRA value: 0.84; mean rank: 1.8), as sclerotherapy as safer option in terms of ovarian response to IVF stimulation. CONCLUSIONS: The present NMA fails to support the effectiveness of any option to treat hydrosalpinx before IVF in order to improve live birth rates, although the beneficial effect of salpingectomy and US aspirations on ongoing pregnancy rates and of both salpingectomy and LTO on clinical pregnancy rates emerges from our analysis, which reinforces current recommendations. Based on the aggregated analyses, sclerotherapy could be a promising alternative to conventional laparoscopic techniques, combined with a favorable safety profile. This article is protected by copyright. All rights reserved.

Impact of congenital uterine anomalies on obstetric and perinatal outcomes: systematic review and meta-analysis.

Background: Congenital uterine anomalies (CUA) can be associated with impairments of early and late pregnancy events. Objective: To assess the impact of CUA on reproductive outcomes in pregnancies conceived spontaneously or after assisted reproduction. Materials and Methods: Systematic review and meta-analysis of cohort studies comparing patients with CUA versus women with normal uterus. A structured literature search was performed in leading scientific databases to identify prospective and retrospective studies. The Newcastle-Ottawa scale, adapted to AHRQ standards, was used to assess the risk of bias. Pooled odds ratios (OR) were calculated. Publication bias and statistical heterogeneity were assessed, and meta-regression was used to analyse the heterogeneity. Main outcome measures: Miscarriage, ectopic pregnancy, placental abruption, term, and premature rupture of membranes (PROM), malpresentation at delivery, preterm delivery prior to 37, 34 and 32 weeks, caesarean delivery, intrauterine growth restriction/small for gestational age, foetal mortality and perinatal mortality. Results: 32 studies were included. CUAs increased significantly the risk of first/second trimester miscarriage (OR:1.54;95%CI:1.14-2.07), placental abruption (OR:5.04;3.60-7.04), PROM (OR:1.71;1.34-2.18), foetal malpresentation at delivery (OR:21.04;10.95-40.44), preterm birth (adjusted OR:4.34;3.59-5.21), a caesarean delivery (adjusted OR:7.69;4.17-14.29), intrauterine growth restriction/small for gestational age (adjusted OR:50;6.11-424), foetal mortality (OR:2.07;1.56-2.73) and perinatal mortality (OR:3.28;2.01-5.36). Conclusions: CUA increases the risk of complications during pregnancy, delivery, and postpartum. Complications most frequent in CUA patients were preterm delivery, foetal malpresentation, and caesarean delivery. What is new?: Bicornuate uterus was associated with the highest number of adverse outcomes, followed by didelphys, subseptate and septate uterus.

Muscle architectural properties indicate a primary role in support for the pelvic limb of three-toed sloths (Bradypus variegatus).

Tree sloths evolved below-branch locomotion making them one of few mammalian taxa beyond primates for which suspension is nearly obligatory. Suspension requires strong limb flexor muscles that provide both propulsion and braking/support, and available locomotor kinetics data indicate that these roles differ between fore- and hindlimb pairs. Muscle structure in the pelvic limb is hypothesized to be a key anatomical correlate of function in braking/support during suspensory walking and propulsion and/or support during vertical climbing. This expectation was tested by quantifying architecture properties in the hindlimb limb musculature of brown-throated three-toed sloths (Bradypus variegatus: N = 7) to distinguish the roles of the flexor/extensor functional muscle groups at each joint. Measurements of muscle moment arm (rm ), mass, belly length, fascicle length, pennation angle, and physiological cross-sectional area (PCSA) were taken from n = 45 muscles. Overall, most muscles studied show properties for contractile excursion and fast joint rotational velocity. However, the flexor musculature is more massive (p = 0.048) and has larger PCSA (p = 0.003) than the extensors, especially at the knee joint and digits where well-developed and strong flexors are capable of applying large joint torque. Moreover, selected hip flexors/extensors and knee flexors have modified long rm that can amplify applied joint torque in muscles with otherwise long, parallel fascicles, and one muscle (m. iliopsoas) was capable of moderately high power in B. variegatus. The architectural properties observed in the hip flexors and extensors match well with roles in suspensory braking and vertical propulsion, respectively, whereas strong knee flexors and digital flexors appear to be the main muscles providing suspensory support in the pelvic limb. With aid in support by the forelimbs and the use of adaptive slow locomotion and slow muscle fiber recruitment patterns, structure-function in the tensile limb systems of sloths appears to collectively represent an additional mechanism for energy conservation.

A Horse of a Different Color?: Tensile Strength and Elasticity of Sloth Flexor Tendons.

Tendons must be able to withstand the tensile forces generated by muscles to provide support while avoiding failure. The properties of tendons in mammal limbs must therefore be appropriate to accommodate a range of locomotor habits and posture. Tendon collagen composition provides resistance to loading that contributes to tissue strength which could, however, be modified to not exclusively confer large strength and stiffness for elastic energy storage/recovery. For example, sloths are nearly obligate suspenders and cannot run, and due to their combined low metabolic rate, body temperature, and rate of digestion, they have an extreme need to conserve energy. It is possible that sloths have a tendon "suspensory apparatus" functionally analogous to that in upright ungulates, thus allowing for largely passive support of their body weight below-branch, while concurrently minimizing muscle contractile energy expenditure. The digital flexor tendons from the fore- and hindlimbs of two-toed (Choloepus hoffmanni) and three-toed (Bradypus variegatus) sloths were loaded in tension until failure to test this hypothesis. Overall, tensile strength and elastic (Young's) modulus of sloth tendons were low, and these material properties were remarkably similar to those of equine suspensory "ligaments." The results also help explain previous findings in sloths showing relatively low levels of muscle activation in the digital flexors during postural suspension and suspensory walking.

Los tendones deben ser capaces de soportar las fuerzas de tracción generadas por los músculos para proporcionar apoyo evitando el fracaso. Por lo tanto, las propiedades de los tendones en las extremidades de los mamíferos deben ser apropiadas para acomodar una serie de hábitos locomotores y postura. La composición del colágeno de tendón proporciona resistencia a la carga que contribuye a la resistencia del tejido que, sin embargo, podría ser modificada para no conferir exclusivamente gran resistencia y rigidez para el almacenamiento/recuperación de energía elástica. Por ejemplo, los perezosos son tirantes casi obligatorios y no pueden funcionar, y debido a su baja tasa metabólica combinada, temperatura corporal y tasa de digestión, tienen una necesidad extrema de conservar energía. Es posible que los perezosos tengan un tendón «aparato suspensor¼ funcionalmente análogo al de los ungulados verticales, lo que permite un soporte en gran medida pasivo de su peso corporal por debajo de la rama, al tiempo que minimiza el gasto de energía contráctil muscular. Los tendones flexores digitales de las patas delanteras y traseras de los perezosos de dos dedos (Choloepus hoffmanni) y de tres dedos (Bradypus variegatus) fueron cargados en tensión hasta que no se probando esta hipótesis. En general, la resistencia a la tracción y el módulo elástico (de Young) de los tendones perezosos eran bajos, y estas propiedades materiales eran notablemente similares a las de los "ligamentos" suspensivos equinos. Los resultados también ayudan a explicar los hallazgos anteriores en perezosos que muestran niveles relativamente bajos de activación muscular en los flexores digitales durante la suspensión postural y la marcha suspensiva.

Increased trophoblast expression of NFAT5/TonEBP in pre-eclamptic placentas and hyperosmolar-treated BeWo cells.

OBJECTIVES: To assess the concentrations of inositol and sorbitol, and determine the expression of related osmolyte factors [nuclear factor of activated T cells 5, also known as tonicity responsive binding protein (NFAT5/TonEBP); sodium myo-inositol transporter (SLC5A3); and aldose reductase] in placentas of pre-eclamptic (PE) patients and trophoblast BeWo cells subjected to hypertonic stress in vitro. STUDY DESIGN: Control and PE placentas were collected. BeWo cells were cultured and subjected to a hyperosmolar solution for 4h. Western blot analysis was performed on NFAT5, SLC5A3, aldose reductase and ERK proteins. High-performance liquid chromatography was used to determine the levels of inositol and sorbitol in cell lysates. RESULTS: Compared with control placentas, PE placentas showed higher levels of inositol and NFAT5, and lower levels of SLC5A3. Treated BeWo cells showed higher levels of inositol, sorbitol, NFAT5 total protein, SLC5A3 and aldose reductase, and increased ERK activation compared with control BeWo cells. CONCLUSIONS: Hyperosmolar conditions increase the expression of NFAT5 in PE placentas and BeWo cells, and may account for the increased osmolyte levels. NFAT5 may accomplish this through aldose reductase and SLC5A3 in trophoblast cells.

Decreased expression of phosphorylated placental heat shock protein 27 in human and ovine intrauterine growth restriction (IUGR).

INTRODUCTION: Intrauterine growth restriction (IUGR) has been documented to increase placental apoptosis at term. HSP27 has been shown to be involved in the control of apoptosis. Our objective is to determine the expression of phosphorylated HSP27 (p-HSP27) in human IUGR, and to determine the role of HSP27 during gestation in an ovine hyperthermia induced model of IUGR. METHODS: Human placenta tissue samples were collected at term to quantify p-HSP27. Pregnant sheep were placed in hyperthermic (HT) conditions to induce IUGR. Placental tissues were collected at 55 (early), 95 (mid-gestation) and 130 (near-term) days gestational age (dGA) to determined phosphorylated and total HSP27 across the development of IUGR. RESULTS: Phosphorylated HSP27 was significantly reduced in human placenta IUGR compared to controls at term. HSP27 was increased throughout gestation during the development of IUGR in the sheep. P-HSP27 was increased in early gestation (55 dGA), and decreased near term (130 dGA). The near term decrease was localized to the trophoblast cells of the placenta. DISCUSSION AND CONCLUSION: We conclude that decreased p-HSP27 at term is present when placental apoptosis is increased during IUGR. This could be a factor leading to the decreased placental weight observed during IUGR.

[The fetal ultrasonography in the second quarter: interest for the pediatric surgeon]. / La ecografía fetal en el segundo trimestre: interés para el cirujano pediatra.

INTRODUCTION: The paediatric surgeon should know the details of prenatal ultrasound diagnosis to participate in advising parents about the continuation of the pregnancy, and to plan the prenatal and postnatal treatment. Our objectives are: to determine the incidence of congenital anomalies detected with ultrasound in the 2nd trimester, the number of these diagnoses which is confirmed at birth and what is the usefulness of this test when advising parents. PATIENTS AND METHODS: We reviewed the prenatal ultrasound in 2nd trimester reports made from January 2005 to July 2009. We note the ultrasound findings, the maternal and gestational age. The evolution of anomalies of the fetuses and the number of spontaneous and volunteers abortions are noted. Finally, the diagnoses are checked in the newborns. RESULTS: 10,256 ultrasonographies are made in this period. 209 stories of pregnant women (2%), which present fetal pathology amenable to general surgical treatment, are accessible for study. These include: 182 urologic disorders (85.44%), 13 digestive disorders (6.1%), 6 thoracic disorders (2.8%), 6 multiple malformations (2.8%), 4 maxillofacial disorders (1.88%) a sacrococcygeal teratoma (0.47%), an umbilical cord cyst (0.47%), 7 pregnancies are spontaneous abortion and 7 are terminated voluntarily. 183 stories of newborns are reviewed, we can confirm 48 uropathies (26.37%), 4 digestive malformations (30.77%), 4 thoracic disorders (66.66%), 2 maxillofacial disorders (50%) and 1 teratoma. CONCLUSIONS: Ultrasonography in the 2nd trimester detects almost 2% of specific fetal malformations. False positives are common in all diagnostic groups. The number of abortions and the terminations of pregnancy is low, most of them are polymalformated fetuses. We believe that ultrasonography in the 20th week have low value to counsel the termination of pregnancy, because only 7 of the 160 terminations indicated in our hospital during the study period, correspond to fetuses with pathology detected in the 2nd trimester. We recognize the usefulness of this test but, the false positive and favorable developments in a high percentage of fetuses, make us to be cautious to advise the continuation of pregnancy and the indication of treatment.

Urinary albumin excretion is associated with true resistant hypertension.

Resistant (or refractory) hypertension (RH) is a clinical diagnosis based on blood pressure (BP) office measurements. About one third of subjects with suspected RH have indeed pseudo-resistant hypertension and 24-h ambulatory-blood pressure-monitoring aids to precisely identify them. Our aim was to determine those clinical, laboratory or echocardiographic variables that may be associated with subjects with sustained hypertension (namely true RH). We carried out a cross-sectional analysis of 143 patients consecutively enrolled with the clinical diagnosis of RH. All patients underwent clinical-demographic, laboratory evaluation, 2D-echocardiography and 24-h ambulatory-blood pressure-monitoring. Pseudo-resistant hypertension or white-coat RH was defined if office BP was > or =140 and/or 90 mm Hg and 24-h BP <130/80 mm Hg. One-hundred and three (72%) patients had true RH and 40 (28%) patients had white-coat RH. True RH patients had significantly higher diabetes prevalence and higher office-systolic blood pressure (SBP) levels. Regarding target organ damage, left ventricular mass index (LVMI) and 24-h urinary albumin excretion (UAE) were also higher in true RH after adjustment for possible confounders (P=0.031 and P=0.012, respectively). In a logistic regression analysis, only office-SBP (multivariate OR (95%CI): 1.030 (1.003-1.057), P=0.030) and UAE (multivariate OR (95% CI): 2.376 (1.225-4.608), P=0.010) were independently associated with true RH. We conclude that true resistant hypertension is associated with silent target organ damage, especially UAE. In patients with suspected RH, assessment of 24 h ambulatory BP is the most accurate way to detect a population with high risk for target-organ damage.

Switching to nevirapine decreases insulin levels but does not improve subcutaneous adipocyte apoptosis in patients with highly active antiretroviral therapy-associated lipodystrophy.

Subcutaneous adipocyte apoptosis occurs in lipotrophic areas of patients with highly active antiretroviral therapy (HAART)-associated lipodystrophy. Fourteen patients with HAART-associated lipodystrophy had 2 subcutaneous biopsies for evidence of adipocyte apoptosis, the second after a randomized change to nevirapine (n=8) or after remaining on a regimen of indinavir-based HAART (n=6). Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP-digoxigenin nick end-labeling method. Patients who were switched to nevirapine had a significant decrease in insulinemia and a significant increase in the glucose:insulin ratio. Overall, subcutaneous adipocyte apoptosis increased in 3 patients who were switched to nevirapine and in 3 who continued to receive indinavir but decreased in 2 patients switched to nevirapine and another 2 who continued to receive indinavir. Subcutaneous adipocyte apoptosis continues to occur in lipotrophic areas of patients with HAART-associated lipodystrophy despite switching from indinavir to nevirapine, suggesting that such a strategy will be useless for reversal of lipoatrophy.

Xanthomas of the Achilles tendon: report of a bilateral case and review of the literature.

We report a case of bilateral Achilles tendon xanthoma as the first clinical manifestation of familial hypercholesterolemia. We review the literature and stress the need for orthopaedic surgeons to be familiar with this disease. An early diagnosis of this metabolic disorder is important to institute medical therapy and to alter the course of the disease before the onset of coronary artery disease.

Comparison of treatment utilization and outcome for Hispanics and non-Hispanic whites.

OBJECTIVE: To examine the use of formal alcohol treatment and Alcoholics Anonymous (AA) by Hispanics and non-Hispanic whites, and to compare ethnic groups on posttreatment functioning. METHOD: Data from a publicly funded substance abuse treatment center in New Mexico were used to investigate possible differences between Hispanic (n = 46) and non-Hispanic white (n = 62) men (n = 76) and women (n = 32) on percent days alcohol therapy and AA attendance for 6 months after study recruitment. RESULTS: Hispanic clients were more often male (80% vs 63%), had fewer years of education (mean = 11.6 vs 12.6) and were less likely to live alone (7% vs 29%) than were non-Hispanic white clients. The heavy drinking (drinks per drinking day mean = 16.7; standard drink units in prior 90 days mean = 941.00) and few abstinent days (mean = 0.44) that characterized both groups at intake improved over time with Hispanics engaging in more formal alcohol therapy sessions but attending fewer AA meetings than non-Hispanic whites over the course of 6 months of follow-up. Attendance at treatment and AA were separately associated with decreased intensity and quantity of alcohol use, but not abstinent days, for both ethnic groups. CONCLUSIONS: Hispanic and non-Hispanic white clients used somewhat different treatment strategies to deal with alcohol-related problems, these paths, however, ultimately resulted in similar posttreatment drinking outcomes (frequency, intensity and quantity of alcohol consumption).

Alcohol, drug use and consequences among Hispanics seeking treatment for alcohol-related problems.

OBJECTIVE: Ethnic differences in alcohol consumption patterns are often reported in general population surveys, but less is known about variation among ethnic groups presenting for treatment. METHOD: Within a larger clinical trial, patterns of drinking, drug use and related problems were compared for Hispanic (n = 102) and non-Hispanic white (n = 104) male (n = 154) and female (n = 52) clients presenting at a public clinic for outpatient treatment of alcohol problems. RESULTS: Relatively few reliable ethnic differences were observed in alcohol /drug use patterns. Non-Hispanic white men reported significantly more pretreatment tobacco use than did Hispanic men (84.7% vs 61.3% of past 90 days). Hispanic women reported significantly fewer legal problems (28.6% vs 83.9%), symptoms of dependence and negative consequences of drinking relative to non-Hispanic white women. Measures of acculturation and acculturative stress failed to differentiate drinking patterns among Hispanic clients. CONCLUSIONS: Within a treatment-seeking sample, Hispanics and non-Hispanics may be more similar with regard to drinking practices than is the case in the general population. High consumption, adverse consequences and dependence symptoms were characteristic of men presenting for alcohol treatment regardless of ethnic identification. In contrast, Hispanic treatment-seeking women had the lowest consumption, adverse consequences and dependence symptoms of all the groups described, and they reported significantly fewer alcohol-related problems and symptoms than did non-Hispanic women.

Efficiency of different enrichment and isolation procedures for the detection of Salmonella serotypes in edible offal.

Rapid detection systems for Salmonella in foodstuffs are currently being developed. However, existing standards still call for application of traditional methods employing pre-enrichment followed by selective enrichment and isolation. The efficacy of various methods was tested using 264 chicken and lamb organ meats. Pre-enrichment was carried out in Tryptone Soy Broth (TSB) and enrichment in Tetrathionate Brilliant Green Broth (TTB) at 37 degrees C, Selenite Broth with Brilliant Green and Sulphapyridine at 37 degrees C and 43 degrees C, and Rappaport-Vassiliadis Broth (RV 10) at 42 degrees C. The isolation media were Brilliant Green Agar (BGA), Deoxycholate Citrate Agar, Hektoen Enteric Agar (HEA) and Salmonella-Shigella Agar. Enrichment in RV/42 degrees C followed by isolation on BGA as recommended by ISO standard no. 6579 and enrichment in TTB/37 degrees C followed by isolation in HEA, no longer recommended by that standard, produced the best results. Low percentages of positive samples and difficulties in detecting Salmonella are the result of interference by competing organisms (Enterobacteriaceae) and the number of salmonellas present after enrichment. A total of 528 samples (TSB, eggs, lamb liver and chicken liver) were inoculated with Salm. enteritidis, Salm. kapemba and Salm. virchow, and the preceding experiment was repeated. All the TSB and egg samples tested positive, but the percentage of positive samples from the lamb and chicken liver was only 81-92%. Recovery of the salmonellas did not depend upon the method employed or the serotype inoculated but instead on interference by competing flora and the numbers of Salmonella present in the samples.

Selective action of inhibitors used in different culture media on the competitive microflora of Salmonella.

The action of 12 inhibitors employed in the culture media used to detect the presence of Salmonella in food on 24 bacterial strains including contaminating Gram-positive bacteria common in water and food, Gram-negative bacteria, especially Enterobacteriaceae and Pseudomonadaceae, which are components of the competitive microflora, and six Salmonella serotypes was tested. Two liquid culture media (AR 5 and AE 1) were used. Series of tubes containing increasing concentrations of each inhibitor were inoculated with the test strains and incubated at 37 degrees C until growth was verified spectrophotometrically (24-48 h). The results showed that the inhibitors were effective against the Gram-positive contaminating microflora. They did not preferentially inhibit the competitive microflora of Salmonella, chiefly Enterobacteriaceae, and were ineffective against the Pseudomonas strains, which can tolerate concentrations higher than those customarily employed in culture media.

Effect of L-asparaginase on insulin secretion from isolated rat islets of Langerhans.

The effects of L-asparaginase were evaluated on glucose-induced insulin release from isolated rat islets of Langerhans. Islets were obtained by enzymatic digestion of pancreas from Sprague-Dawley rats. The study of L-asparaginase effects on insulin secretion was performed in a static incubation of islets. Insulin secretion was measured at 60 min of incubation with different secretagogues with and without L-asparaginase. L-Asparaginase at concentrations from 310 to 5,000 U/ml could inhibit the glucose-induced insulin secretion in a dose-dependent manner. This effect was not recovered after incubation in the absence of the drug for another 2 h. The half-maximal inhibitory effect of the enzyme on insulin secretion was observed at L-asparaginase concentrations of 1,000 U/ml. Tolbutamide (200 microM) and ketoisocaproic acid (20 mM) did not induce insulin secretion in the presence of moderately high L-asparaginase concentrations. L-Asparaginase did not inhibit glucose-induced insulin secretion in the presence of isobutyl-methyl-xanthine (IBMX) (20 microM) or forskolin (20 microM). L-Asparaginase promoted a decrease in total c-AMP in isolated rat islets at concentrations from 500 to 1,500 U/ml when they were stimulated by glucose. If islets were treated with IBMX or forskolin, L-asparaginase did not inhibit the glucose-induced total c-AMP levels in islets.

Caloric test with oculogyral illusion as response.

It has been demonstrated that the caloric test can be simplified further by making use of the oculogyral illusion. Since the test is conducted under conditions of optic fixation, this method probably also enhances the sensitivity of the caloric test. The reproducibility of the tests also appears high, at least in respect of measures of "canal paresis". When used in conjunction with other tests for detecting vestibular imbalance, e.g. examination for spontaneous and provocation nystagmus using Frenzel glasses, this OGI caloric test should provide a convenient procedure for the clinical examination of vestibular function.