Effectiveness of a childbirth massage programme for labour pain relief in nulliparous pregnant women at term: a randomised controlled trial.

INTRODUCTION: The effect of massage for pain relief during labour has been controversial. This study investigated the efficacy of a programme combining intrapartum massage, controlled breathing, and visualisation for non-pharmacological pain relief during labour. METHODS: This randomised controlled trial was conducted in two public hospitals in Hong Kong. Participants were healthy low-risk nulliparous Chinese women ≥18 years old whose partners were available to learn massage technique. Recruitment was performed at 32 to 36 weeks of gestation; women were randomised to attend a 2-hour childbirth massage class at 36 weeks of gestation or to receive usual care. The primary outcome variable was the intrapartum use of epidural analgesia or intramuscular pethidine injection. RESULTS: In total, 233 and 246 women were randomised to the massage and control groups, respectively. The use of epidural analgesia or pethidine did not differ between the massage and control groups (12.0% vs 15.9%; P=0.226). Linear-by-linear analysis demonstrated a trend whereby fewer women used strong pharmacological pain relief in the massage group, and a greater proportion of women had analgesic-free labour (29.2% vs 21.5%; P=0.041). Cervical dilatation at the time of pethidine/epidural analgesia request was significantly greater in the massage group (3.8 ± 1.7 cm vs 2.3 ± 1.0 cm; P<0.001). CONCLUSION: The use of a massage programme appeared to modulate pain perception in labouring women, such that fewer women requested epidural analgesia and a shift was observed towards the use of weaker pain relief modalities; in particular, more women in the massage group were analgesic-free during labour.

Diastolic dysfunction grading, echocardiographic and electrocardiogram findings in 50 patients with apical hypertrophic cardiomyopathy.

INTRODUCTION: Apical Hypertrophic Cardiomyopathy (Apical HCM) is an uncommon variant of hypertrophic cardiomyopathy, but it is relatively more common in Asian countries. This is a retrospective, non-randomised, single centre study of patients with Apical HCM focusing on their diastolic dysfunction grading, echocardiographic parameters and electrocardiograms (ECG). METHODS: All Apical HCM patients coming for clinic visits at the Institut Jantung Negara from September 2017 to September 2018 were included. We assessed their echocardiography images, grade their diastolic function and reviewed their ECG on presentation. RESULTS: Fifty patient were included, 82% (n=41) were males and 18% (n=9) females. The diastolic function grading of 37 (74%) patients were able to be determined using the updated 2016 American Society of Echocardiography (ASE) diastolic guidelines. Fifty percent (n=25) had the typical ace-ofspades shape left ventricle (LV) appearance in diastole and 12% (n=6) had apical pouch. All patients had T inversion in the anterior leads of their ECG, and only 52% (n=26) fulfilled the ECG left ventricular hypertrophy (LVH) criteria. Majority of our patients presented with symptoms of chest pain (52%, n=26) and dyspnoea (42%, n=21). CONCLUSION: The updated 2016 ASE guideline makes it easier to evaluate LV diastolic function in most patients with Apical HCM. It also helps in elucidating the aetiology of dyspnoea, based on left atrial pressure. Clinicians should have a high index of suspicion for Apical HCM when faced with deep T inversion on ECG, in addition to a thick LV apex with an aceof- spades appearance during diastole.

Echocardiographic and electrocardiographic presentations of patients with endomyocardial biopsy-proven cardiac amyloidosis.

OBJECTIVE: Cardiac amyloidosis is under diagnosed and its prevalence is unknown. This is a retrospective, nonrandomised, single centre study of patients with endomyocardial biopsy-proven cardiac amyloidosis focusing on their echocardiographic and electrocardiogram (ECG) presentations. This is the first case series in Malaysia on this subject. METHODS: We identified all of our endomyocardial biopsyproven cardiac amyloidosis patients from January 2010 to January 2018 and reviewed their medical records. All patients echocardiographic and ECG findings reviewed and analysed comparing to basic mean population value. RESULTS: In total there are 13 biopsy-proven cardiac amyloidosis patients. All of the biopsies shows light chain (AL) amyloid. Majority of the patients (8, 61.5%) is male, and most of our patients (8, 61.5%) is Chinese. All seven patients on whom we performed deformation imaging have apical sparing pattern on longitudinal strain echocardiogram. Mean ejection fraction is 49.3%, (SD=7.9). All patients have concentric left ventricular hypertrophy and right ventricular hypertrophy. Diastolic dysfunction was present in all of our patients with nine out of 13 patients (69.2%) having restrictive filling patterns (E/A ≥2.0 E/e' ≥15). On electrocardiogram, 12 (92%) patients have prolonged PR interval (median 200ms, IQR 76.50ms) and 9 (69.2%) patients have pseudoinfarct pattern. CONCLUSION: Echocardiography plays an important role in diagnosing cardiac amyloidosis. The findings of concentric left ventricular hypertrophy with preserved ejection fraction without increased in loading condition should alert the clinician towards its possibility. This is further supported by right ventricular hypertrophy and particularly longitudinal strain imaging showing apical sparing pattern.

Host genetic variants of ABCB1 and IL15 influence treatment outcome in paediatric acute lymphoblastic leukaemia.

BACKGROUND: Host germline variations and their potential prognostic importance is an emerging area of interest in paediatric ALL. METHODS: We investigated the associations between 20 germline variations and various clinical end points in 463 children with ALL. RESULTS: After adjusting for known prognostic factors, variants in two genes were found to be independently associated with poorer EFS: ABCB1 T/T at either 2677 (rs2032582) or 3435 (rs1045642) position (P=0.003) and IL15 67276493G/G (rs17015014; P=0.022). These variants showed a strong additive effect affecting outcome (P<0.001), whereby patients with both risk genotypes had the worst EFS (P=0.001), even after adjusting for MRD levels at the end of remission induction. The adverse effect of ABCB1 T/T genotypes was most pronounced in patients with favourable cytogenetics (P=0.011) while the IL15 67276493G/G genotype mainly affected patients without common chromosomal abnormalities (P=0.022). In both cytogenetic subgroups, increasing number of such risk genotypes still predicted worsening outcome (P<0.001 and=0.009, respectively). CONCLUSION: These results point to the prognostic importance of host genetic variants, although the specific mechanisms remain unclarified. Inclusion of ABCB1 and IL15 variants may help improve risk assignment strategies in paediatric ALL.

Mycobacterium fortuitum catheter-related sepsis in acute leukaemia.

We report Mycobacterium fortuitum (M. fortuitum) catheter-related sepsis in a five-year-old boy with acute lymphoblastic leukaemia (ALL). This is the first reported case of M. fortuitum infection seen in our paediatric oncology patients. The patient was in haematological remission and receiving maintenance chemotherapy via an indwelling central venous catheter (Port-a-Cath). He was febrile, toxic-looking and was in respiratory distress. Clinically, he had a right pleural effusion and gross hepatomegaly. The patient was lymphopaenic and had deranged liver function test. Repeat paired blood cultures were positive for M. fortuitum. The catheter was promptly removed and he was treated aggressively with intravenous amikacin, cefoxitin, ciprofloxacin, trimethoprim-sulfamethoxazole and oral clarithromycin, with good clinical response. The patient remained well without further complications while on chemotherapy. M. fortuitum is an uncommon cause of catheter-related infection in patients with malignancies. Removal of an infected catheter is necessary for complete control of atypical mycobacterial infection in an immunosuppressed patient.

Closed versus partially ventilated endotracheal suction in extremely preterm neonates: physiologic consequences.

This randomized cross over study aimed to compare the severity and incidences of desaturation and bradycardia between the partially ventilated endotracheal suction method (PVETS) and closed tracheal suction system (CTSS) in extremely preterm neonates. Fifteen intubated and ventilated extremely low birth weight preterm infants (mean birth weight 689g) randomly underwent both suction techniques within a 12-h period to obtain a paired reading group. The process was repeated 24-48h apart until three pairs of reading groups were collected. Changes in oxygen saturation measured with pulse oximetry and heart rate changes measured with electrocardiogram were recorded using Hewlett-Packard m240A monitor trending software. The mean of each parameter's variation from baseline was obtained using SPSS descriptive statistics and analyzed using SPSS repeated measures ANOVA. Fisher Exact Test was used to analyze the incidence of desaturation and bradycardia. The closed tracheal suction system reported a significantly smaller degree of oxygen saturation fall (P<0.005) and significantly fewer incidences of desaturation. There was also a significantly smaller degree of heart rate reduction although episodes of bradycardia were not significantly different between the two methods. Oxygen saturation and heart rate were significantly more stable during the use of CTSS compared to PVETS in the extremely low birth weight preterm population.

Functional connections of the rat medial cortex and basal forebrain: an in vivo intracellular study.

Projections between the medial cortex and basal forebrain in the rat were demonstrated by intracellular recordings and the anterograde tracer Phaseolus vulgaris leucoagglutinin. Direct projections between these areas were indicated by antidromic action potentials, short latency (less than 5 ms) orthodromic potentials, and labeled axon terminals in the basal forebrain subsequent to iontophoresis of Phaseolus vulgaris leucoagglutinin into posterior cingulate cortex. High proportions of antidromic action potentials were encountered in responsive cortical neurons (66%) and basal forebrain neurons (97%). Antidromic latencies recorded in the basal forebrain (less than 1.0 ms) revealed fast ascending projections; cortical neurons showed both fast and slow descending projections (latencies of 0.3-3.7 ms). Relatively few synaptic potentials (none in the diagonal band of Broca) and sparse labeling of axon terminals observed in the basal forebrain indicated that the ascending projections may be the more physiologically important or, at least, densest pathway. Polysynaptic feedforward pathways were suggested through long latency (greater than 20 ms) inhibitory and excitatory postsynaptic potentials, the former being the more common response. Candidate inhibitory neurons were identified in both cortex and basal forebrain. Possible monosynaptic (less than 5 ms) inhibitory postsynaptic and antidromic responses in these cells provided evidence that candidate inhibitory neurons participate in the reciprocal pathways.

Nociceptin/orphanin FQ modulation of rat midbrain dopamine neurons in primary culture.

Previous microdialysis studies have identified a suppressive effect of the novel opioid peptide nociceptin (also known as orphanin FQ) on dopamine release from mesolimbic neurons. In order to further evaluate the locus of this action, we investigated nociceptin's action in an in vitro model system, namely midbrain dopamine neurons in primary culture. Immunohistochemical analysis revealed abundant tyrosine hydroxylase- and GABA-immunoreactive neurons, with a strong correlation between tyrosine hydroxylase content and basal endogenous dopamine release. Nociceptin (0.01-100 nM) suppressed basal dopamine release by up to 84% (EC50=0.65 nM). This action was reversible by drug removal and attenuated by co-application of the non-peptidergic ORL1 antagonist, Compound B. Nociceptin had no significant effect on dopamine release evoked by direct depolarization of the terminals with elevated extracellular K+, suggesting that nociceptin suppresses dopamine release by modulating the firing rate of the dopamine neurons. Nociceptin also suppressed GABA release from the cultures (45% maximal inhibition; EC50=1.63 nM). Application of the GABA-A antagonist, bicuculline, elevated extracellular dopamine concentrations but the dopamine release inhibiting property of nociceptin persisted in the presence of bicuculline. The NMDA receptor antagonist, D(-)-2-amino-5-phosphononpentanoic acid (AP-5) had no effect on basal dopamine release and failed to modify nociceptin's inhibitory effects. Thus, nociceptin potently modulates dopamine release from midbrain neurons most likely as a result of a direct suppression of dopamine neuronal activity.

Functional coupling, desensitization and internalization of virally expressed mu opioid receptors in cultured dorsal root ganglion neurons from mu opioid receptor knockout mice.

Although mu opioid receptors desensitize in various cell lines in vitro, the relationship of this change in signaling efficacy to the development of tolerance in vivo remains uncertain. It is clear that a system is needed in which functional mu opioid receptor expression is obtained in appropriate neurons so that desensitization can be measured, manipulated, and mutated receptors expressed in this environment. We have developed a recombinant system in which expression of a flag-tagged mu opioid receptor is returned to dorsal root ganglia neurons from mu opioid receptor knockout mice in vitro. Flow cytometry analysis showed that adenoviral-mediated expression of the amino-terminal flag-tagged mu opioid receptor in neurons resulted in approximately 1.3x10(6) receptors/cell. Many mu opioid receptor cell lines express a similar density of receptors but this is approximately 7x greater than the number of endogenous receptors expressed by matched wild-type neurons. Inhibition of the high voltage-activated calcium currents in dorsal root ganglia neurons by the mu agonist, D-Ala(2), N-MePhe(4), Gly(5)-ol-enkephalin (DAMGO), was not different between the endogenous and flag-tagged receptor at several concentrations of DAMGO used. Both receptors desensitized equally over the first 6 h of DAMGO pre-incubation, but after 24 h the response of the endogenous receptor to DAMGO had desensitized further than the flag- tagged receptor (71+/-3 vs 29+/-7% respectively; P<0.002), indicating less desensitization in neurons expressing a higher density of receptor. Using flow cytometry to quantify the percentage of receptors remaining on the neuronal cell surface, the flag-tagged receptor internalized by 17+/-1% after 20 min and 55+/-2% after 24 h of DAMGO. These data indicate that this return of function model in neurons recapitulates many of the characteristics of endogenous mu opioid receptor function previously identified in non-neuronal cell lines.

Convergence of projections from the rat hippocampal formation, medial geniculate and basal forebrain onto single amygdaloid neurons: an in vivo extra- and intracellular electrophysiological study.

We recorded extra- and intracellular responses from rat amygdaloid neurons in vivo after electrical stimulation of the hippocampal formation (dentate gyrus, hippocampal fields CA3 and CA4, entorhinal cortex, subicular complex); medial geniculate; and basal forebrain (diagonal band, ventral pallidum, olfactory tubercle, nucleus accumbens, bed nucleus of stria terminalis, lateral preoptic area, substantia innominata). Stimulation of hippocampal formation structures evoked IPSPs or EPSP-IPSP sequences in which the IPSP had a lower threshold than the EPSP. Recordings from candidate inhibitory neurons in the amygdala indicated that excitatory afferents from the hippocampal formation contact both amygdaloid inhibitory and principal neurons (feedforward inhibition), and that the inhibitory neurons have a lower threshold of activation. Medial geniculate stimulation also evoked EPSP-IPSP sequences. In marked contrast to these results, stimulation of basal forebrain structures evoked short latency IPSPs in amygdaloid neurons. This provides the first physiological evidence for direct inhibition of the amygdala by the basal forebrain. Basal forebrain stimulation also evoked EPSP-IPSP sequences in amygdaloid neurons. Individual amygdaloid neurons could show responses to stimulation of the hippocampal formation, basal forebrain, and medial geniculate, indicating that synaptic input from these areas converges onto single amygdaloid cells. The findings provide further information about the synaptic organization of afferents to the amygdala, and indicate that single amygdaloid neurons play a role in the synaptic integration of input from these diverse sources.

Functional reciprocal connections of the rat entorhinal cortex and subicular complex with the medial frontal cortex: an in vivo intracellular study.

We used in vivo intracellular recording techniques in the rat in order to determine the properties of projections from the medial frontal cortex to the entorhinal cortex and subicular complex. Three main results were obtained. (1) A high proportion (65%) of neurons within the medial frontal cortex were antidromically activated at short latency (0.4-1.9 ms) by electrical stimulation of the entorhinal cortex or subicular complex. This provided physiological evidence for fast direct projections from the medial frontal cortex to the entorhinal cortex and subicular complex. (2) Clear excitatory postsynaptic potentials (EPSPs) were evoked in 8% of the cells within the entorhinal cortex, subicular complex, or adjacent cortices after electrical stimulation of the medial frontal cortex. (3) The most salient synaptic response was inhibition, as shown by the presence of inhibitory postsynaptic potentials (IPSPs) in 50% of the cells sampled. Similar results were obtained for the reciprocal pathway: 56% of the sampled cells in the entorhinal cortex or subicular complex responded with antidromic spikes to stimulation of the medial cortex; 4% of medial frontal neurons responded to stimulation of the entorhinal cortex or subicular complex with clear EPSPs, and 48% with IPSPs. The latencies of most synaptic responses, 15-25 ms, were inconsistent with monosynaptic activation. This suggests that oligosynaptic relays amplified the signal within or en route to their targets, and/or that cells with more slowly propagating axons were also present but not sampled by the intracellular electrodes. Finally, responsive fast-spiking cells (candidate inhibitory neurons) were encountered within target structures. The results provide evidence that these distant cortical regions are functionally connected in a reciprocal manner, and that both principal and inhibitory neurons are excited by this projection system.

GABAergic synaptic transmission in projections from the basal forebrain and hippocampal formation to the amygdala: an in vivo iontophoretic study.

We recorded extracellular responses from rat amygdaloid neurons in vivo after electrical stimulation of the basal forebrain and hippocampal formation. Iontophoretic application of the GABAA receptor antagonist, bicuculline, lead to the appearance of short latency evoked bursts after stimulation of either region. This occurred whether the baseline response was inhibitory or excitatory. Bicuculline only affected an early phase of inhibition, leaving a longer latency, longer duration phase unchanged or even increased. By contrast, the GABAB receptor antagonist, phaclofen, never produced such short latency evoked bursts. Both bicuculline and phaclofen increased the spontaneous rate of firing of amygdaloid neurons. The excitatory burst response to hippocampal formation stimulation of an amygdaloid candidate inhibitory neuron was blocked by CNQX (an antagonist of the AMPA subtype of glutamate receptor). Based on these and prior studies, it seems likely that the effects of hippocampal formation stimulation are mediated by feed-forward inhibition, in which GABAergic amygdaloid inhibitory neurons are excited by glutamatergic projections from the hippocampal formation. The effects of basal forebrain stimulation may be mediated by both feed-forward inhibition and direct, GABAergic inhibition.

Neurophysiology and neuropharmacology of projections from entorhinal cortex to striatum in the rat.

We studied projections from the entorhinal cortex (Ent) to the striatum in anesthetized rats using extra- and intracellular recording and multibarrel iontophoresis. The majority of recording were from the caudate-putamen (CPu) and core of the nucleus accumbens (AcbC). Electrical stimulation of the Ent evoked synaptic responses in 77% of tests with AcbC neurons and 48% of tests with CPu neurons. In the case of AcbC neurons, 61% of these tests proved to be excitatory and were often followed by inhibitory phases. In contrast to this, only 18% of tests from CPu neurons were excitatory. Intracellular HRP labeling showed that responsive cells were medium spiny neurons. During iontophoretic experiments, application of the glutamatergic AMPA antagonist DNQX could selectively decrease or block excitatory responses. The GABAA antagonist bicuculline methiodide increased cellular firing rates and could reveal excitatory responses, suggesting block of a short-latency, short-duration inhibitory component. Ejection of the GABAB antagonist CGP-35348 could attenuate a later, longer-duration component of inhibition. The results indicate that the Ent excites striatal neurons at least in part by glutamatergic receptors and suggest that this excitation is followed by secondary prolonged GABAergic inhibition.

Lack of Fos-like immunoreactivity after spontaneous seizures or reinduction of status epilepticus by pilocarpine in rats.

Acute seizures and status epilepticus induced by pilocarpine lead to the expression of Fos-like immunoreactivity in several specific brain areas in a manner similar to that of other models of limbic seizures. Upon development of status epilepticus after systemic pilocarpine injection, animals develop a state where chronic spontaneous seizures recur. Assessment of Fos-like immunoreactivity after such spontaneous seizures or after status epilepticus reinduction reveals either lack of staining or a weak reaction in a few brain areas including the ventral tip of the dentate gyrus, prepiriform, lateral piriform and perirhinal cortices, and scattered locations throughout temporal neocortex. Our results suggest that status epilepticus induction may lead to a long-lasting state of Fos down-regulation.

Use of a mixture of medium-chain triglycerides and longchain triglycerides versus long-chain triglycerides in critically ill surgical patients: a randomized prospective double-blind study.

Twenty critically-ill surgical patients who needed total parenteral nutrition were randomly enrolled in a double-blind study comparing two intravenous fat emulsions: one containing a mixture of 50% medium-chain triglycerides and 50% long-chain triglycerides and another containing 100% longchain triglycerides. The purpose of this study was to investigate metabolic and biochemical differences between both emulsions with special reference to liver enzymes. After a baseline period of 24 h with only glucose and NaCl infusion, the lipid emulsion was added continuously during 24 h over 5 days. The parenteral nutrition was administered in mixture bags containing amino-acids, glucose and lipids together. Two-thirds of the non-protein calories were administered as glucose 40% and one third as either long-chain triglycerides or a mixture of medium-chain triglycerides and long-chain triglycerides. The total amount of non-protein calories received was the measured energy expenditure during the baseline period plus 10% and was fixed during the study. Plasma substrate concentrations, energy expenditure, and nitrogen balance were determined and arterial blood samples were taken. No toxic effects or complications attributable to one of the two emulsions were observed. There was no significant difference in energy expenditure, nitrogen balance, liver function tests, carnitine, transferrin, pre-albumin, albumin, cholesterol, triglycerides and free fatty acids. The only parameter that showed a different pattern of reaction between the two emulsions was serum bilirubin concentration. In this study no evidence of any advantageous effect of a mixture of medium-chain triglycerides and long-chain triglycerides was seen.

Carpal tunnel syndrome. An evaluation of the provocative diagnostic tests.

In order to evaluate the usefulness of provocative tests (wrist-flexion test, nerve-percussion test, and tourniquet test) in the diagnosis of carpal tunnel syndrome, the results of provocative testing were evaluated in a group of patients (sixty-seven hands) with electrodiagnostically proved carpal-tunnel syndrome and in a group of fifty control subjects. The sensitivity and specificity of each test were calculated. The wrist-flexion test was found to be the most sensitive while the nerve-percussion test, although least sensitive, was most specific. The tourniquet test was quite insensitive and not very specific, and should not be used as a routine screening test in the diagnosis of carpal tunnel syndrome.

Microcalorimetric study of mitochondria isolated from fish liver tissue.

We determined the thermogenesis curves of mitochondria isolated from fish liver tissue by using an LKB 2277 Bioactivity Monitor. After isolation from the fish liver, mitochondria still have activity and can live for a long time by using the stored nutrients. We calculated the recovery rate constants of mitochondria. We found that the thermogenesis curves of mitochondria are similar to those obtained from prokaryotic cells, but not similar to those obtained from eukaryotic cells. We determined the metabolic thermogenesis curves of mitochondria isolated from two kinds of carp liver tissue, scattered-scaled mirror carp and harvest carp. There are some important similarities and some important differences between these thermogenesis curves.

Free tendon grafting to repair the metacarpophalangeal joint of the thumb. Surgical techniques and a review of 70 patients.

We report the use of a free tendon graft in 70 patients to repair lesions of the capsuloligamentous complex of the metacarpophalangeal joint of the thumb. Of these 37 had a lesion of the ulnar collateral ligament, 18 of the radial collateral and 11 of the volar plate. Four patients had combined lesions. We outline our techniques and review 51 of the patients. Of those 47 (92%) were satisfied, and all but one had regained full stability. Pinch grip strength was normal in 48. About one-third of the patients had some loss of flexion/extension; this was seldom noticed by the patients and caused no significant disability. Free tendon graft reconstruction is indicated for severe fresh lesions, for old lesions with chronic disability and for lesions which have not responded to conservative management.