Decline in Decreased Cephalosporin Susceptibility and Increase in Azithromycin Resistance in Neisseria gonorrhoeae, Canada.

Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010-2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines.

A randomised, double-blind, parallel, placebo-controlled study to evaluate the efficacy of MF 5232 (Mucotrol), a concentrated oral gel wafer, in the treatment of oral mucositis.

OBJECTIVE: Oral mucositis is a major complication of cytotoxic chemotherapy and radiotherapy associated with significant morbidity, pain, odynophagia, dysgeusia and subsequent dehydration and malnutrition, and effective prophylaxis and/or treatment of this condition is essential. The currently available palliative treatment shows improvement only in patients with mild to moderate mucositis. The primary aim of this study was to compare the clinical efficacy of MF 5232 (Mucotrol), a concentrated oral polyherbal gel wafer formulation, with placebo in the management of chemoradiation-induced mucositis in cancer patients. PATIENTS AND DESIGN: In this randomised, double-blind, pilot study a total of 30 patients of either sex with chemoradiation-induced oral mucositis were randomised to receive MF 5232 (n = 15) or a matching placebo (n = 15) after food three times a day for 7-10 days. Patients were evaluated using validated and standardised scoring systems at baseline and after 7-10 days of treatment. RESULTS: There were 11 evaluable patients in each treatment group. There was a significant reduction in mean mucositis scores with MF 5232 as follows: WHO (from 3.0 to 1.8), Radiation Therapy Oncology Group (gross score: from 2.8 to 1.8; functional score: from 2.9 to 1.0), and Objective Scoring System (ulceration score: from 7.4 to 4.4; erythema score: from 13.7 to 7.0). There were no significant changes in scores for placebo recipients. The treatments were well tolerated, with the exception of two patients in the treatment group who reported a burning sensation in the mouth after dissolving the wafer. CONCLUSION: This pilot study provided positive evidence for the efficacy of MF 5232 therapy in chemoradiation-induced mucositis. This was probably a result of its local analgesic, antioxidant and immunomodulatory activity and wound-healing properties. Further in-depth analysis in a larger number of patients is required to confirm these positive results.

External cephalic version at term with tocolysis and vibroacoustic stimulation.

OBJECTIVE: This study compared the obstetric outcome in women who had external cephalic version (ECV) for breech presentation after 36 weeks gestation with those who did not, to see whether ECV reduces breech deliveries and cesarean section rates with reduced complications. METHOD: External cephalic version was attempted in 200 women (study group) with the use of tocolysis and vibroacoustic stimulation. The control group (ECV not attempted) comprised of 278 women with breech presentation after 36 weeks. RESULT: The cesarean section rate was 14.0% in the successful version group compared with 55.2% in the unsuccessful version group. The overall cesarean section rate in the study group was 32.5%. In the control group of 278, the fetus remained in the breech presentation in labor in 269 women with a cesarean section rate of 51.4% which was not different from the unsuccessful version group (55.2%). CONCLUSION: This study supports the randomized trials conducted earlier in that ECV after 36 weeks gestation reduced the number of breech deliveries and cesarean sections (32.5% in the study group compared with 51.4% in the control group) (P > 0.00001).

Effects of hormone deficiency, androgen therapy and calcium supplementation on bone mineral density in female transsexuals.

A total of 79 healthy female transsexuals, divided into four groups, were involved in this study. Group 1 comprised 15 pre-operated normal cycling females; Group 2, five pre-operated females who were on regular androgen therapy for 1-3 years; Group 3, 27 post-operated females who were on regular androgen therapy for 2-12 years; and Group 4, 32 post-operated females who either had stopped or were on irregular androgen therapy. A bone scan of the lumber spine, at positions L2-L4, was carried out for each subject. A blood sample was taken for measurement of plasma testosterone concentrations. Ten subjects from Group 3 had a repeat bone scan following 10-39 months of calcium supplement (625 mg daily as calcium carbonate); another 10 post-operated females of Group 3 had a repeat bone scan 6-59 months later; and five subjects from Group 4 had a repeat scan following resumption of regular androgen therapy for 17-27 months. The mean +/- SE concentrations of testosterone of Groups 1-4 were, respectively, 0.58 +/- 0.05, 10.1 +/- 2.48, 7.7 +/- 0.98 and 0.99 +/- 0.14 ng/ml. Pre-operated females (Group 2) following 1-3 years of regular androgen therapy had significantly higher BMD and age-matched BMD than corresponding levels in pre-operated normal cycling females in Group 1. While the age-matched BMDs of post-operated females, who were on regular androgen therapy, were not significantly different, the mean BMD was significantly lower than corresponding values in the controls of Group 1. Post-operated females in Group 4 had significantly lower BMDs and age-matched BMDs as compared to corresponding values in controls of Group 1. The BMDs and age-matched BMDs of post-operated females, who were on regular androgen therapy, were significantly raised following daily calcium supplementation for durations ranging from 10-39 months. A repeat bone scan carried out following a lapse of 6-59 months did not reveal any significant change in the BMDs and age-matched BMDs of 10 post-operated females on regular androgen therapy. On the other hand, the BMDs and age-matched BMDs of post-operated females in Group 4 were significantly raised following the resumption of regular androgen therapy for 17-27 months. Results of the present study showed that ovariectomy and remaining in the hormone-deficient state for a sufficiently long duration was associated with a definite loss of bone mass. However, it was shown in this study that the resumption of regular androgen therapy for a sufficient duration could arrest this loss and, additionally, substantially increase the bone mass. Androgen appears to have a potentially greater impact on bone mass than oestrogen. Furthermore, calcium supplementation in a Singaporean population, which is accustomed to a low dietary calcium intake, can assist in the accretion of a higher bone mass in an adult population.

Audible in utero sound caused by the ultrasonic radiation force from a real-time scanner.

While investigating in utero sound levels during vibro-acoustic stimulation on the maternal abdomen it was noticed that noise level increased when the real-time ultrasonic scanner beam was directed at the sensing hydrophone. The noise was recorded and later analysed for frequency content and waveform. It appeared related to the scanning and frame rate frequencies of the scanner used. Sounds may originate from radiation pressure produced when the ultrasound beam is absorbed by tissue or reflected from bone or the metal hydrophone. This implies that although ultrasound cannot be heard per se, any modulation of its intensity will produce vibrations in the maternal tissues or reflecting structures such as skull bone, and especially stapes, malleus and incus, that would be heard as sound by the fetus. The intensity of the sound produced varied with orientation of the transducer beam and this may itself produce a stimulation. Based on our recordings (Fig. 1), it was calculated (please see Appendix) that the fetus would hear a sound corresponding to 84dB noise pressure level in air.

Search for the most predictive tests of fetal well-being in early labor.

The aim of the study was to evaluate the admission CTG alone and in combination with the following tests: fetal acoustic stimulation test (FAST), maternal perception of sound provoked fetal movement (mpSPFM), amniotic fluid index (AFI), and umbilical artery doppler studies in early labor. 1092 singleton pregnancies in cephalic presentation, and with intact amniotic membranes at 37 weeks gestation or more, were admitted in early labor to the labor ward at the National University Hospital, Singapore. Admission tests were performed, and labor managed according to established labor ward protocol. Of all the tests performed, only the results of the admission CTG and color of the amniotic fluid were known to the obstetrician. If the admission CTG is normal, AFI is > 5 cm and there is an acceleratory responses to FAST the incidence of fetal distress is low. In the presence of a reactive admission CTG and in the absence of thick meconium, fetal heart rate response to FAST and the AFI provided a better selection of the high risk fetus that would require closer monitoring or early delivery. When the admission CTG was suspicious, FAST, AFI, and blood flow velocity waveform studies may allow more confident prediction of the ability of the fetus to withstand the stresses of labor.

Cloning, nucleotide sequence and expression of the bifunctional dihydrofolate reductase-thymidylate synthase from Glycine max.

cDNAs encoding the bifunctional dihydrofolate reductase-thymidylate synthase from Glycine max were isolated and sequenced. The 1794 base full length cDNA contains a single open reading frame of 1593 bases. The predicted size of the encoded protein is 530 amino acids with a molecular weight of 59,707. The protein has two domains: a 226 residue DHFR domain in the N-terminus, which is over 30% identical to human DHFR or the DHFR domain of protozoal DHFR-TS, and a 304 residue thymidylate synthase (TS) domain, which is over 60% identical to eukaryotic TS enzymes. The whole protein sequence is greater than 75% identical to DHFR-TS sequences from two other plants, Daucus carota and Arabidopsis thaliana. The sequence of two tryptic peptides obtained from DHFR preparations matched the predicted amino acid sequence, one peptide lying in the DHFR domain and the other in the TS domain. These results indicate that DHFR and TS exist in a bifunctional polypeptide in Glycine max. The coding region of the cDNA was inserted downstream of the T7 promoter and translation initiation signals in the vector pET-3a. This construct (pDR-TS) was transformed into Escherichia coli BL21 (DE) [plysS] which produces T7 RNA polymerase upon induction by isopropyl-beta-D-thiogalactopyranoside (IPTG). The expression of the bifunctional enzyme was confirmed by detection of both DHFR and TS activities. The purified enzyme has a subunit molecular mass of 60 kDa. This is the first report of expression of a plant DHFR-TS cDNA.

Differential regulation of cholesterol side-chain cleavage (P450scc) and aromatase (P450arom) enzyme mRNA expression by gonadotrophins and cyclic AMP in human granulosa cells.

The co-ordinated biosynthesis of progesterone and oestradiol in the human ovary is critical for reproductive cyclicity and eventual pregnancy. The crucial regulatory enzymes for progesterone and oestradiol biosynthesis in granulosa cells are the cholesterol side-chain cleavage (P450scc) and aromatase (P450arom) enzymes respectively. We utilized the cDNA sequences encoding P450arom and P450scc to examine the roles of FSH and LH, and their intracellular second messenger, cyclic AMP (cAMP), in regulating steroidogenic gene expression. Mature granulosa cells (aspirated before the onset of the endogenous LH surge) and granulosa lutein cells (obtained after an ovulatory dose of human chorionic gonadotrophin) were cultured for 4 days with FSH, LH or dibutyryl cAMP (dbcAMP). After the period of culture, total RNA was extracted from granulosa cells and Northern analyses were performed utilizing 32P-labelled cDNAs encoding P450arom and P450scc. Spent culture media were analysed for steroid and cAMP content. Both FSH and LH strongly stimulated P450arom mRNA expression and oestradiol production in mature granulosa cells. On the other hand, P450scc mRNA expression and progesterone biosynthesis were weakly induced by FSH; maximal synthesis occurred only in the presence of LH. With both gonadotrophins at equivalent concentrations, LH generated a 30-fold higher level of cAMP than FSH. Furthermore, the differential effects of FSH and LH on P450 mRNA expression were reproduced by the presence of low and high concentrations of dbcAMP respectively. LH (and high levels of dbcAMP) increased P450arom mRNA expression in mature granulosa cells but inhibited its accumulation in granulosa lutein cells. In contrast, it stimulated P450scc mRNA expression and progesterone synthesis in both mature granulosa and granulosa lutein cells. Therefore, FSH/low cAMP levels stimulated P450arom gene expression and oestradiol production, while LH/high cAMP levels maximally induced P450scc gene expression and function, in a development-related manner consistent with steroid production in vivo. These findings support the hypothesis that one set of genes (like P450arom) in human granulosa cells is regulated by FSH/low cAMP levels and another (like P450scc) by LH/high cAMP levels.

Should assessment of amniotic fluid volume form an integral part of antenatal fetal surveillance of high risk pregnancy?

This study was conducted to evaluate the role of the Amniotic Fluid Index (AFI), used along with nonstress cardiotocography (NST) and fetal acoustic stimulation test (FAST), when required, in prediction of adverse pregnancy outcome. Over a 3-year period 565 pregnant women had antepartum fetal surveillance due to various high risk pregnancy factors and delivered within 7 days of the test. Antepartum fetal surveillance included nonstress cardiotocography together with estimation of AFI. Need for induction of labour, presence of meconium at rupture of membranes, Caesarean section for fetal distress, Apgar score at 5 minutes, need for neonatal endotracheal intubation, admission to neonatal special care unit and perinatal death were the main outcome measures. Nonreactive nonstress tests and Caesarean sections for fetal distress were more common and neonatal outcome was significantly poorer in patients with AFI < 5 cm than in those with higher AFI values. Of the 4 perinatal deaths in the group with AFI < 5 cm, 3 had a reactive NST within 7 days of fetal death. It is concluded that pregnancy outcome is often poor in the presence of very low AFI and in these cases a reactive NST loses its usual reassuring value. It is suggested that AFI estimation should be included as an integral part of antepartum fetal surveillance of high risk pregnancies.

Computerised cardiotocography following vibro-acoustic stimulation.

To study the effect of vibro-acoustic stimulation (VAS) to the mean fetal heart rate (FHR), period of high and low FHR variation, overall variation (msec and bpm) and short term variation (msec). In a prospective study 17 pregnant women between 34-42 weeks gestation admitted to antenatal ward for obstetric complications two 60 min FHR recording was carried out with an interval of 30 min in between recordings. On a random basis the fetus was stimulated by a vibro-acoustic stimulator for 5 sec at the beginning of one of the two 60 min FHR recordings. Automated analysis of the FHR, tocodynamometry, and maternal perception of fetal movements was done by a commercially available computerized programme (System 8000). It was possible to obtain the two 60 min recordings with signal loss of < 10% in 12 out of 17 patients. No changes were observed when the FHR parameters for 60 min after VAS was compared with the control period. When analyzed in segments of 0 to 10, 11 to 20, 20 to 40 and 41 to 60 min the mean baseline FHR was significantly higher after VAS during the first 10 minutes compared with any 10 or 20 min segment of the control period or any such segments 10 min after VAS. Concomitantly the overall variation and short-term variation was significantly lower during the first 10 minutes following VAS (p < 0.05) compared with the parameters in the corresponding periods during the control period.(ABSTRACT TRUNCATED AT 250 WORDS)

Vibroacoustic stimulation and intrauterine sound pressure levels.

The sound pressure level in amniotic fluid generated by vibroacoustic stimulation, assessed with a hydrophone placed close to the fetal head, was studied in 16 subjects. The mean recorded sound pressure level was 115 dB and the highest level was 129 dB. The range of the background noise was 63.5-80.5 dB. There was no obvious relationship between the distance from the stimulator to the hydrophone and the intrauterine sound pressure level. Although sound pressure levels are high, they are probably reduced before reaching the cochlea of the fetus because of the surrounding amniotic fluid and the fluid in the middle ear.

No evidence of hearing loss due to fetal acoustic stimulation test.

The fetal acoustic stimulation test is used increasingly for fetal assessment. To evaluate the possibility of acoustic trauma, 465 children who had been exposed to vibroacoustic stimulation in utero were screened at 4 years of age for high-frequency hearing loss. A hand-held audiometer with test tones at 25 dB for 1000 and 4000 Hz was used because responses at this level indicate hearing within normal limits for middle and high frequencies. Thirty-one children failed the test. Failure to respond was followed by inspection of the ear canal for wax, tympanometry, and reflex measurement to assess the tympanic membrane, middle ear, and eustachian tube. Hearing was retested across the full frequency range using conventional audiometric technique, and referral for otolaryngologic examination and treatment was made if necessary. The causes of hearing loss were impacted wax in 12, current or recent upper respiratory tract infection with eustachian tube dysfunction and middle ear effusion in 15, and unresolved middle ear effusion after treatment with antibiotics for otitis media in two. Profound bilateral sensorineural hearing loss of unknown origin was found in one and slight bilateral gently sloping hearing loss in another. Retesting of all children with conductive hearing loss indicated that hearing had returned to normal after treatment. None of the children showed evidence of hearing loss.

The gonadotrophin surge in humans: its mechanism and role in ovulatory function--a review.

The presence of the positive feedback by oestrogen resulting in the mid-cycle gonadotrophin surge in women distinguishes the female's feedback control of gonadotrophin secretion from that in males. The gonadotrophin surge is an event crucial for final oocyte maturation, ovulation and subsequently for corpus luteum function. In this article, the roles of oestrogen, progesterone and testosterone in the regulation of the gonadotrophin surge are reviewed. Evidences appear to support the suggestion that an oestradiol pulse of sufficient potency and lasting for an adequately long duration alone is sufficient to trigger off the LH surge. Progesterone has a biphasic effect on LH secretion, and although not required for the initiation of the LH surge, may play a role in maintaining the LH peak. Testosterone, on the other hand, does not modulate the LH surge mechanism in man. Dysfunction of the gonadotrophin surge mechanism may account for some forms of ovulatory disorders: amenorrhoea and in some cases of delayed or precocious puberty. In patients with polycystic ovary syndrome (PCOS), different degrees of dysfunction of the gonadotrophin surge mechanism have been shown.

Effectiveness of transcutaneous electric nerve stimulator for pain relief in labour.

The effectiveness of transcutaneous electric nerve stimulation (TENS) for pain relief in labour was compared to inhalation analgesia consisting of 50% nitrous oxide and 50% oxygen (ENTONOX). In the first part of the study 101 patients in early labour were allocated to using TENS (Group A) or ENTONOX (Group B) for pain relief. Our results did not show any beneficial effect on pain relief in labour with the use of TENS over ENTONOX; 18.8% of patients in Group A went through labour without any further form of analgesia as opposed to 17.0% in Group B. In the second part of the study 20 nulliparous patients having induced labour were randomly allocated to use TENS (Group C) or ENTONOX (Group D) as the first modality of pain relief. A switchover was made when labour pains were no longer tolerable. The results showed that both TENS and ENTONOX could be used in early labour up to 5-6 cm cervical dilatation till the frequency of contractions was nearly 5 in 10 min or the first 3-4 hr from the time patients first requested pain relief in labour when frequency of contractions was nearly 4 in 10 min. TENS could be used in early labour for patients who wish to be ambulant and is as effective as ENTONOX. Either modality of pain relief was not adequate for pain relief throughout labour.

Lack of correlation of selenium level in human semen with sperm count/motility.

Considering the importance of selenium (Se) in male fertility, its concentration was measured in 211 semen samples from 211 normozoospermic, oligozoospermic, asthenozoospermic, and azoospermic men using the hydride generation atomic absorption spectrophotometry. No significant correlation of any kind existed between Se level in the seminal plasma and sperm count or motility. In view of the known poor correlation of these two frequently used semen parameters with the incidence of pregnancy, the assessment of the fertilizing potential of normozoospermic ejaculates with low Se levels is warranted.

Evaluation of maternal perception of sound-provoked fetal movement as a test of antenatal fetal health.

Maternal perception of sound-provoked fetal movement was correlated with the results of nonstress cardiotocography in 1097 women with obstetric or medical antenatal risk factors. Ninety-two percent of the mothers felt fetal movements with the stimulus; all but three had a reactive non-stress test (NST). These three women were taking multiple antihypertensive drugs and were less than 33 weeks' gestation. Of 88 patients with no maternal perception of sound-provoked fetal movement, ten had nonreactive NSTs. Ultrasound confirmed the absence of fetal movement to the stimulus. The outcome in nine of these ten cases suggested some evidence of fetal compromise. Maternal perception of sound-provoked fetal movement correlated well with the results of the NST; the sensitivity (76.9%), specificity (92.8%), and negative predictive value (99.7%) were all high, although the positive predictive value was only 11.4%. Maternal perception of sound-provoked fetal movement may suffice as an inexpensive and simple method of evaluating antenatal fetal well-being in risk situations. When the mother is doubtful or does not feel the sound-provoked fetal movement, NST is indicated to evaluate the fetal health.

Amniotic fluid selenium status in pre-eclampsia.

Selenium levels were measured in amniotic fluid samples obtained from 60 normal pregnant and 40 pre-eclamptic women closely matched for age and gestation using the hydride generation technique coupled with atomic absorption spectroscopy. The mean +/- SD levels in the normal and pre-eclamptic groups were 6.8 +/- 3.7 and 6.7 +/- 2.2 ng/ml, respectively. The difference in the values of amniotic fluid selenium between these two groups of patients was not statistically significant (p greater than 0.5).

Selenium status in pregnancy: studies in amniotic fluid from normal pregnant women.

Selenium concentrations were determined in amniotic fluid samples obtained from 111 healthy normal pregnant women (median age, 27.5 years) between 12 and 42 weeks of gestation using hydride generation technique coupled with atomic absorption spectroscopy. There was a gradual decrease in the amniotic fluid selenium concentration with the progress of pregnancy. The negative correlation between the gestational age and amniotic fluid selenium concentration was highly significant (p less than 0.001). The implications of these findings in normal pregnancy are discussed.