Maternal and fetal anaesthesia for fetal surgery.

Over the last three decades, advances in early diagnosis of fetal anomalies, imaging and surgical techniques have led to a huge expansion in fetal surgery. A small number of specialist centres perform fetal surgery, which involves high-risk anaesthesia for the mother and fetus. The anaesthetist plays an integral role within the large multispecialty and multidisciplinary team, involved in planning and delivering care for complex surgical procedures. This article reviews three fetal surgical procedures, congenital diaphragmatic hernia, myelomeningocele repair and ex-utero intrapartum treatment for airway obstruction. The underlying fetal pathology, surgical management, anaesthetic considerations and risks for both the mother and fetus are described for each. Fundamental to this is the understanding that clear communication and collaboration between all team members is vital to ensure successful outcomes of patients, the mother and the fetus.

Higher risk of opioid-induced respiratory depression in children with neurodevelopmental disability: a retrospective cohort study of 12 904 patients.

BACKGROUND: Children with neurodevelopmental disabilities may be at risk of opioid-induced respiratory depression. We aimed to quantify the risks and effectiveness of morphine nurse-controlled analgesia (morphine-NCA) for postoperative pain in children with neurodevelopmental disabilities. METHODS: We carried out a retrospective cohort study of 12 904 children who received postoperative i.v. morphine-NCA. Subjects were divided into a neurodevelopmental disability group and a control group. Rates of clinical satisfaction, respiratory depression, and serious adverse events were obtained, and statistical analysis, including multilevel logistic regression using Bayesian inference, was performed. RESULTS: Of 12 904 patients, 2390 (19%) had neurodevelopmental disabilities. There were 88 instances of respiratory depression and 52 serious adverse events; there were no opioid-related deaths. The cumulative incidence of respiratory depression in the neurodevelopmental disability group was 1.09% vs 0.59% in the control group [odds ratio 1.8 (98% chance that the true odds ratio was >1)]. A significant interaction between postoperative morphine dose and neurodevelopmental disabilities was observed, with higher risk of respiratory depression with increasing dose. Satisfaction with morphine-NCA was very high overall, although children with neurodevelopmental disabilities were 1% more likely to have infusions rated as fair or poor (3.3 vs 2.1%, χ2P<0.001). CONCLUSIONS: Children with neurodevelopmental disabilities were 1.8 times more likely to suffer respiratory depression, absolute risk difference 0.5%; opioid-induced respiratory depression in this group may relate to increased sensitivity to dose-relate respiratory effects of morphine. Morphine-NCA as described was an acceptable technique for children with and without neurodevelopmental disabilities.

Short communication: Detection of stx2 and elt genes in bovine milk by using a multiplex PCR system.

The aim of this study was to detect 2 important toxin genes from diarrheagenic Escherichia coli (DEC) in bovine milk using a new multiplex PCR. To standardize the multiplex PCR, the stx2 and elt genes were investigated for the detection of Shiga toxin-producing Escherichia coli (STEC) and enterotoxigenic E. coli (ETEC), respectively. The DNA template was prepared with a thermal procedure (boiling) and a commercial kit. Samples consisted of UHT and pasteurized milk, both skimmed, and STEC and ETEC were tested in concentrations between 101 and 109 cfu/mL. With the thermal procedure, the multiplex PCR system detected both pathotypes of E. coli at 109 cfu/mL in UHT and pasteurized milk. When the commercial kit was used for template preparation, STEC and ETEC could be detected at concentrations as low as 104 cfu/mL in UHT and pasteurized milk. Negative controls (Listeria monocytogenes, Salmonella Typhimurium, Salmonella Enteritidis, and Escherichia coli strain APEC 13) were not amplified with the multiplex PCR. These results indicate that the multiplex PCR was a rapid (less than 6 h) and efficient method to detect STEC and ETEC in milk using different methods for DNA preparation; however, the commercial kit was more sensitive than the thermal procedure.

Validation of the Airway-Dyspnoea-Voice-Swallow (ADVS) scale and Patient-Reported Outcome Measure (PROM) as disease-specific instruments in paediatric laryngotracheal stenosis.

OBJECTIVE: To validate the Airway-Dyspnoea-Voice-Swallow (ADVS) instrument as a disease-specific Patient-Reported Outcome Measure in paediatric laryngotracheal stenosis. DESIGN: Prospective observational study. SETTING: A quaternary referral centre for complex airway disease. PARTICIPANTS: Forty-eight patients (30 males) with a mean age of 49 ± 49 months who underwent laryngotracheal surgery or microlaryngoscopy and bronchoscopy (MLB) following laryngotracheal surgery. MAIN OUTCOME MEASURES: Airway-Dyspnoea-Voice-Swallow summary scale and Patient-Reported Outcome Measure (PROM), Paediatric Quality of Life (PedsQL) scale, Paediatric Voice Handicap Index (pVHI) and Lansky performance scale were administered to patients before and 6-8 weeks following airway examination/surgery. RESULTS: Most patients (73%) had intubation-related subglottic stenosis, and 60% of patients had prior airway treatments. The majority of patients (77%) had more than one major chronic morbidity, and the commonest procedures were diagnostic MLB (49%), followed by airway dilation (29%). Cronbach-α value for the ADVS PROM was 0.71 overall and 0.85, 0.86 and 0.64 for the dyspnoea, voice and swallow domains, respectively. Rank correlations between Dyspnoea, Voice and Swallow summary scale and PROM scores were 0.83, 0.71 and 0.81, respectively (P < 0.0001). For those patients undergoing diagnostic MLB, pre- and post-examination scores were highly correlated (intraclass correlations >0.75). There was a significant rank correlation between ADVS PROM score and Lansky performance score (r = -0.68; P < 0.0001). There were significant correlations between PROM score and PedsQL (r = -0.57; P < 0.0001) and between voice domain of the PROM and pVHI (r = 0.78; P < 0.0001). There were strong correlations between Myer-Cotton stenosis severity and dyspnoea scale and PROM score (r = 0.68; P < 0.0001). There were significant differences in voice and swallow ADVS scales and PROM scores between patients with and without concomitant laryngeal/oesophageal pathology. Patient age and presence of high dyspnoea and swallowing PROM scores were independently associated with poorer quality of life and performance status. CONCLUSIONS: These series of observations validate the ADVS instrument as a disease-specific outcome measure for paediatric laryngotracheal stenosis. Dyspnoea and swallowing dysfunction appear to have the greatest impact on quality of life. More widespread adoption of the ADVS instrument could help create a shared language for outcomes communication and benchmarking for children with this complex condition.

A III-nitride nanowire solar cell fabricated using a hybrid coaxial and uniaxial InGaN/GaN multi quantum well nanostructure.

III-Nitride nanowires are currently considered as next generation photovoltaic materials due to their excellent physical properties together with reduced dislocation densities, increased surface area and thus enhanced light absorption and direct path for carrier transport. Here, we investigate the photovoltaic characteristics of a solar cell fabricated from a novel hybrid nanostructure comprising uniaxial and coaxial InGaN/GaN multi-quantum wells (MQWs) along with an InGaN nano-cap layer. Various characterization methods were employed to study the optical and structural properties of the hybrid nanostructure. Transmission electron microscopy images revealed the hybrid nanostructure consists of distinct uniaxial and coaxial InGaN/GaN MQWs along with the InGaN nano-cap layer. The InGaN/GaN MQW architectures have a significant effect on the performance of the photovoltaic device. The solar cell fabricated with the hybrid nanostructure exhibits superior photovoltaic performance compared to the uniaxial as well as the coaxial InGaN/GaN nanowire MQW structures. The improved photovoltaic characteristic is primarily attributed to the considerably larger InGaN active area grown in the hybrid nanostructure. A conversion efficiency of 1.16% along with a fill factor of 70% was obtained for the device fabricated with the hybrid nanostructure. This study provides an experimental demonstration of the improvement of III-nitride nanowire based solar cells incorporating uniaxial and coaxial InGaN/GaN MQWs.

Classification of breast masses in mammograms using genetic programming and feature selection.

Mammography is a widely used screening tool and is the gold standard for the early detection of breast cancer. The classification of breast masses into the benign and malignant categories is an important problem in the area of computer-aided diagnosis of breast cancer. A small dataset of 57 breast mass images, each with 22 features computed, was used in this investigation; the same dataset has been previously used in other studies. The extracted features relate to edge-sharpness, shape, and texture. The novelty of this paper is the adaptation and application of the classification technique called genetic programming (GP), which possesses feature selection implicitly. To refine the pool of features available to the GP classifier, we used feature-selection methods, including the introduction of three statistical measures--Student's t test, Kolmogorov-Smirnov test, and Kullback-Leibler divergence. Both the training and test accuracies obtained were high: above 99.5% for training and typically above 98% for test experiments. A leave-one-out experiment showed 97.3% success in the classification of benign masses and 95.0% success in the classification of malignant tumors. A shape feature known as fractional concavity was found to be the most important among those tested, since it was automatically selected by the GP classifier in almost every experiment.

Interactions of berberine with poly(A) and tRNA.

The interaction of berberine chloride with poly(A) and tRNA has been studied by various spectroscopic techniques. Binding parameters determined from spectrophotometric and spectrofluorimetric measurements by Scatchard analysis indicate a very high effective binding capacity of berberine to poly(A) as compared to DNA or tRNA. The circular dichroism studies show that binding of berberine to poly(A) causes a significant change in the circular dichroic spectrum of poly(A) itself, as manifested by (i) a decrease of both positive and negative bands and (ii) appearance of a conservative type of extrinsic circular dichroic spectrum in the wavelength range of 300-400 nm, while it does not cause any significant alteration to the A form structure of tRNA. It is concluded that berberine interacts stronger with poly(A) than DNA or tRNA. The results are interpreted in terms of its reported biological activities.

Opioid analgesia in the newborn.

Pain in neonates is now well established. Studies of the developmental neurobiology of pain have revealed that pain processing in the immature is very different from that in the mature nervous system. Neonates undergo considerable maturation of peripheral, spinal and supraspinal afferent pain transmission over the early postnatal period but are able to respond to tissue injury with specific behaviour and with autonomic, hormonal and metabolic signs of stress and distress. Opioid analgesia is now widely used in neonates. There is evidence that morphine requirements may be low in the youngest patients. Sensory threshold testing in rat pups has shown that the analgesic potency of systemic morphine mechanical stimulation is significantly greater in the neonate and declines with postnatal age. The changing morphine sensitivity in the postnatal period may be part of a general reorganisation in the structure and function of primary afferent synapses, neurotransmitter/receptor expression and function and excitatory and inhibitory modulation from higher brain centres. Importantly opioid receptor expression undergoes significant developmental regulation - mu opioid receptors, observed to be exuberantly expressed in the neonatal rat, have been found to be functional. These findings have important implications for the human neonate as they provide a possible explanation for the differences in morphine requirements observed in the youngest patients. The study of the underlying mechanisms of pain and analgesia in development has enabled important changes in clinical practice. However, pain in the newborn remains poorly understood and continued research and intensive study in this area is essential for further effective analgesic intervention and the discovery of new targets for therapy.

An innovation in insert visual reinforcement audiometry in children.

Visual reinforcement audiometry (VRA) is an important behavioural test of hearing in young children. The use of insert earphones during VRA provides a reliable method of obtaining ear- and frequency-specific data. Two testers are usually required for this procedure. The first tester operates the audiometer and other controls while the second tester distracts the child with various toys. The paper describes a technique of providing a visual cue to the second tester when a sound stimulus is introduced through the insert earphones.

Binding of sanguinarine to deoxyribonucleic acids of differing base composition.

The binding of the alkaloid sanguinarine to natural DNAs of differing GC content has been studied by spectrophotometry and viscometry techniques. Binding parameters determined from spectrophotometric measurements by Scatchard analysis, according to an excluded-site model, indicate a very high specificity of sanguinarine binding to GC rich DNA. In the strong binding region, the increase of contour length of DNA depends strongly on its base composition, being larger with GC rich DNA than with AT rich DNA. It is concluded that the alkaloid binds preferentially to the GC pairs in DNA template.

Thermodynamics of the interaction of aristololactam-beta-D-glucoside with DNA. Ionic strength dependence of enthalpy and entropy.

The interaction of aristololactam-beta-D-glucoside with calf thymus DNA has been studied by measuring the changes in the absorbance of the alkaloid over a wide range of temperatures and sodium chloride concentrations. The binding parameters obtained are best fit by the neighbour exclusion model. The salt and temperature dependence of the binding constants are used to estimate the thermodynamic parameters involved in the interaction of the alkaloid with DNA. It is observed that aristololactam-beta-D-glucoside binding to DNA is an exothermic process over the entire range of salt and temperature, and the estimated values of enthalpy and entropy change are strongly dependent on the ionic strength of the solution. The enthalpy and entropy changes compensate one another to produce a relatively small Gibbs' free energy change. The possibility that aristololactam-beta-D-glucoside exists as a monovalent cation at neutral pH and the possible molecular contribution to the enthalpy and entropy changes of the aristololactam-beta-D-glucoside-DNA complex are discussed.

Aristololactam-beta-D-glucoside. A new DNA binding monofunctional intercalating alkaloid.

The binding of aristololactam-beta-D-glucoside to DNA is characterized by hypochromism and bathochromism in the absorption band, quenching of the fluorescence intensity, increase in the positive and negative ellipticity of DNA, enhancement of thermal transition temperature, sign and magnitude of thermodynamic parameters, increase of the contour length of sonicated rod-like DNA and induction of the unwinding-rewinding process of covalently closed superhelical DNA. Binding parameters determined from absorbance and fluorescence titration by Scatchard analysis, according to an excluded-site model, indicate a very high affinity towards DNA. The binding of the alkaloid is an exothermic process with Gibbs free energy of -7.4 kcal/mol, van't Hoff enthalpy of -13.8 kcal/mol and entropy of -21.5 cal/degree/mol at 25 degrees. On the basis of these observations it is concluded that aristololactam-beta-D-glucoside binds to DNA by a mechanism of intercalation.

Detection of hepatitis B virus DNA by polymerase chain reaction in vaccinated and non-vaccinated Senegalese children.

An hepatitis B immunization programme was initiated in Senegal in 1978, and infants included in this controlled study have been followed for a period of 2-12 years after immunization. During this period HBV infections have been observed both in vaccinated and non-vaccinated infants. The polymerase chain reaction was used to search for HBV DNA sequences in the sera of 153 children with evidence of serum markers of past or present HBV replication. Amplified HBV DNA sequences were detected in 93% of the HBsAg positive individuals, in 58% of those only positive for antiHBc antibodies and in 7.8% of antiHBs and antiHBc positive infants. The results confirm the high efficiency and long-lasting effectiveness of HB vaccine.

Testosterone and aggression in children.

OBJECTIVE: A link between serum testosterone and aggressive behavior, which has been demonstrated in numerous animal studies and suggested in several studies of adult men, has never been investigated in children before the time of puberty. METHOD: We measured serum testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) in 18 highly aggressive prepubertal boys, ages 4 to 10, hospitalized for violent or unmanageable behavior at a state children's psychiatric facility in New York City (the Bronx). We compared them with a group of age and race matched controls from the same demographic area, screened negative for aggressive behavior problems. All the aggressive subjects met DSM-III-R criteria for conduct disorder and scored higher than the 98th percentile on the aggression subscale of the Child Behavior Checklist (mean T = 80 for the group). RESULTS: There were no significant differences between aggressive and nonaggressive children for T, SHBG, DHEA, DHEAS, or ratios of combinations of these variables. CONCLUSIONS: These findings raise questions about inferences from adult studies that testosterone may play a causal role in the development of human aggression. Testosterone does not appear to be a useful biological marker for aggressivity in early childhood.

Photophysical property of sanguinarine in the excited singlet state.

The photophysical property of the alkanolamine form of sanguinarine has been studied in aqueous and organic medium under various environmental conditions from the measurement of absorption, fluorescence and NMR spectroscopy. Alkanolamine fluorescence shows an excitation time dependent fluorescence quenching and the rate of quenching increases significantly with increasing pH and concentration of the species, while it decreases with increasing temperature. This phenomenon is explained by excited state intramolecular proton transfer from a 6-OH group to the lone pair of nitrogen through the formation of zwitterion.

Circular dichroism of sanguinarine-DNA complexes: effect of base composition, pH and ionic strength.

The interaction of sanguinarine with various naturally occurring and synthetic deoxyribonucleic acids of different base composition and sequence has been studied from the measurement of circular dichroism spectroscopy in buffer of various ionic strengths and pH values where physico-chemical properties of DNA remain unchanged. Binding of sanguinarine to DNA causes a change in the circular dichroism spectrum of DNA itself by showing the increase of both positive and negative bands and appearance of a broad positive band with peak at 340 nm. All systems studied exhibit extrinsic positive band that is independent of DNA base composition and sequence. Calf thymus DNA-sanguinarine complexes in different salt concentrations show that, at saturation, the magnitude of molar ellipticity at 340 nm increases with decreasing sodium ions concentration. Sanguinarine-DNA complexes in buffer of various pH values also show that the molar ellipticity at 340 nm is greater in acidic pH and lower in alkaline pH. It is concluded that the alterations of secondary structure of DNA upon binding of sanguinarine is maximum in buffer of low ionic strength and acidic pH and the number of bound alkaloid molecules per base pair, at saturation, is more in G-C rich DNA than in A-T rich DNA.

Isaptent--a new cervical dilator.

A new cervical dilator, Isaptent, was prepared from granulated Plantago ovata (Isapgol) seed husk. It was evaluated in a multicentric clinical trial for dilatation of the cervix in subjects opting for medical termination of pregnancy. The trial covered 804 women in over 21 centres in different parts of the country. The cases were between 15 to 45 years of age, 0 to 10 parity with a gestation period of 8 to 24 weeks. A single tent was used in 750 subjects and satisfactory dilatation was achieved in 94% of the cases. The cervical dilatation bore no relationship to age, parity and gestation period of the subjects. The tent provided self-lubrication, caused no apparent damage to the cervix and the vaginal flora remained unchanged in the randomly selected subjects in whom bacteriologic studies were performed. The outcome of the clinical trial and advantages of Isaptent over the other procedures used for cervical dilatation are discussed.

Effect of various organic compounds on synthesis of glucoamylase by an isolated strain Penicillium italicum.

Yeast extract (0.5%) stimulates the production of glucoamylase and cell synthesis while methylene blue (0.1 mM) activates the synthesis of glucoamylase. Studies on the metabolic changes during fermentation of glucoamylase in a selected medium by P. italicum show that the rate of production of glucoamylase and cellular growth are greatly accelerated between 48 and 168 hr. Rapid growth of cells during this period may account for enhanced utilization of maltose and NH4NO3 from the medium. The acid production remains constant from 48 to 144 hr. Different forms of nitrogen decrease steadily. Although methylene blue stimulates the production of glucoamylase in the broth it has practically no effect on the rate of utilization of amino and total nitrogen from the broth.

Interaction of berberine chloride with deoxyribonucleic acids: evidence for base and sequence specificity.

The interaction of berberine chloride with natural and synthetic DNAs of differing base composition and sequences was followed by various spectroscopic and viscometric studies. The binding of berberine chloride was characterized by hypochromism and bathochromism in the absorption bands, enhancement of fluorescence intensity, stabilization against thermal denaturation, perturbations in the circular dichroic spectrum, increase in the contour length of sonicated rod-like DNA and induction of unwinding-rewinding process of covalently closed superhelical DNA, depending on the base composition and sequences of base pairs. Binding parameters determined from absorbance and fluorescence titration by Scatchard analysis, according to an excluded-site model, indicated a very high specificity of berberine to AT-rich DNAs and alternate AT polymer. Fluorescence quantum yield was maximum for the complexes with AT-rich DNAs and alternate AT polymer. Taken together, these results suggest that berberine chloride exhibits considerable specificity towards alternating AT polymer and binds to AT-rich DNAs by a mechanism of classical intercalation.