Prenatal diagnosis of beta-thalassaemia in Pakistan: experience in a Muslim country

A service for prenatal diagnosis of beta-thalassaemia was introduced in Pakistan in May 1994. Two renowned Islamic scholars, consulted before the service was introduced, ruled that a pregnancy can be terminated if the fetus is affected by a serious genetic disorder, and if termination is before 120 days (17 weeks) of gestation. During the first 3(1/2) years of the service 300 couples requested the test. Almost all the couples had been informed by their treating doctors. Most diagnoses were made between 10 and 16 weeks of gestation, and only 15 (5%) were reached after the 16th week. DNA analysis was by the amplification refractory mutation system (ARMS). A multiplex ARMS was developed in which three primer combinations identified the mutations in 91.5% of the couples. In 13 couples (4. 3%) linkage analysis was required for the fetal diagnosis. In 47/53 (88.7%) women carrying an affected fetus the pregnancy was terminated. In six cases it was declined principally on religious grounds. Postnatal confirmation of the prenatal diagnosis was possible in 117 unaffected children. One year after the start of the service, interviews with 141 couples with an affected child showed that 72% knew of the availability of prenatal diagnosis. Thirty-two of the informed couples had had a pregnancy, but only 18 (56%) used prenatal diagnosis. The main reasons for non-utilization of prenatal diagnosis were the cost of the test and fear of undergoing the test, though some gave no clear explanation. This study demonstrates that prenatal diagnosis is feasible and acceptable in a Muslim country such as Pakistan.     

Spermine alkaloids from Schweinfurthia papilionacea

Two new macrocylic alkaloids, 11-epi-ephedradine A (11-epi-orantine) [1] and schweinine [2], were isolated from the whole plant of Schweinfurthia papilionacea, in addition to (-)-ephedradine A (orantine) [3]. Their structures were determined by spectroscopic means, and the stereochemistry has been assigned on the basis of 2D nmr techniques.     

Hyperbaric vs. isobaric bupivacaine for spinal anaesthesia for elective caesarean section: a Cochrane systematic review

Both isobaric and hyperbaric bupivacaine have been used for spinal anaesthesia for elective caesarean section, but it is not clear if one is better than the other. The primary objective of this systematic review was to determine the effectiveness and safety of hyperbaric bupivacaine compared with isobaric bupivacaine administered during spinal anaesthesia for elective caesarean section. We included 10 studies with 614 subjects in the analysis. There was no evidence of differences either in the risk of conversion to general anaesthesia, with a relative risk (95%CI) of 0.33 (0.09–1.17) (very low quality of evidence), or in the need for supplemental analgesia, the relative risk (95%CI) being 0.61 (0.26–1.41) (very low quality of evidence). There was also no evidence of a difference in the use of ephedrine, the amount of ephedrine used, nausea and vomiting, or headache. Hyperbaric bupivacaine took less time to reach a sensory block height of T4, with a mean difference (95%CI) of ?1.06 min (?1.80 to ?0.31). Due to the rarity of some outcomes, dose variability, use of adjuvant drugs and spinal technique used, future clinical trials should look into using adequate sample size to investigate the primary outcome of the need for supplemental analgesia.     

Mediation of swim-stress antinociception by the opioid delta 2 receptor in the mouse.

The present study has characterized the antinociceptive response to cold water swim-stress (CWSS) in mice using opioid-selective antagonists as well as tolerance and cross-tolerance approaches. Mice subjected to CWSS using water at 5 degrees C for 3 min showed a marked antinociceptive response in the tail-flick test, which reached approximately 90% after +10 min, and which persisted for 15 to 20 min. This antinociceptive response (at +10 min) was antagonized by naloxone or by the delta antagonist ICI 174,864. Additionally, the CWSS response was antagonized by the opioid delta 2 antagonist, naltrindole-5'-isothiocyanate, but not by the delta 1 antagonist, [D-Ala2,Leu5,Cys6]enkephalin, or by the mu antagonist, beta-funaltrexamine or by the kappa antagonist, norbinaltorphimine. Although the CWSS-induced antinociceptive effect was blocked by some delta antagonists and tolerance resulted from the CWSS-induced response, the decrease in body temperature after each CWSS exposure was not affected by the opioid antagonists and reliably occurred in CWSS-tolerant mice, suggesting that the observed antinociception was independent of changes in body temperature. In mice rendered tolerant to the antinociceptive actions of the mu agonist, [D-Ala2,NMPhe4,Gly-ol] enkephalin, or to [D-Pen2,D-Pen5]enkephalin (predominantly a delta 1 agonist), the CWSS-induced antinociceptive response was unaltered. In contrast, in mice tolerant to the delta 2 agonist, [D-Ala2,Glu4]deltorphin, the CWSS-induced antinociceptive response was markedly and significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Specific targeting and noninvasive magnetic resonance imaging of an asthma biomarker in the lung using polyethylene glycol functionalized magnetic nanocarriers

Simultaneous inhibition of IL4 and IL13 via the common receptor chain IL4Rα to block adequately their biologic effects presents a promising therapeutic approach to give the additional relief required for asthma patients. In this study, superparamagnetic iron oxide nanoparticles were conjugated with anti‐IL4Rα blocking antibodies via polyethylene glycol (PEG) polymers. The delivery of these blocking antibodies to the inflammatory sites in the lung via the developed nanocarriers was assessed using noninvasive free‐breathing pulmonary MRI. Biocompatibility assays confirmed the safety of the developed nanocarriers for pre‐clinical investigations. For all the investigated formulations, nanocarriers were found to be very stable at neutral pH. However, the stability noticeably decreased with the PEG length in acidic environment and thus the loaded antibodies were preferentially released. Immunofluorescence and fluorimetry assays confirmed the binding of the nanocarriers to the IL4Rα asthma biomarker. Pulmonary MRI performed using an ultra‐short echo time sequence allowed simultaneous noninvasive monitoring of inflammatory responses induced by ovalbumin challenge and tracking of the developed nanocarriers, which were found to colocalize with the inflammatory sites in the lung. Targeting of the developed nanocarriers to areas rich in IL4Rα positive inflammatory cells was confirmed using histological and flow cytometry analyses. The anti‐IL4Rα‐conjugated nanocarriers developed here have been confirmed to be efficient in targeting key inflammatory cells during chronic lung inflammation following intrapulmonary administration. Targeting efficiency was monitored using noninvasive MRI, allowing detection of the nanocarriers’ colocalizations with the inflammatory sites in the lung of ovalbumin‐challenged asthmatic mice. Copyright © 2015 John Wiley & Sons, Ltd.     

The Bath Ankylosing Spondylitis Activity and Function Indices (BASDAI and BASFI) and their correlation with main symptoms experienced by patients with spondyloarthritis

With the aim of assessing whether the Bath Ankylosing Spondylitis Activity and Function Indices (BASDAI and BASFI) are reliable measures of disease activity and function in patients with spondyloarthritides (SpAs), 341 patients with SpA (representing ankylosing spondylitis (14.5%), psoriatic arthritis (27.3%), enteropathic arthritis (6.3%), reactive arthritis (4.9%), and undifferentiated arthritis (46.5%) were asked to complete the BASDAI and BASFI. They were asked to report what their main problems associated with the disease were from a list of seven symptoms: fatigue, neck pain, upper back pain, lower back pain, stiffness, joint pain or swelling, and pain with pressure on joints. Correlations between the main symptoms experienced by patients with SpAs and the indices, defined by Spearman’s correlation coefficient, showed that BASDAI best correlated with neck pain [BASDAI 2 and total BASDAI score correlate strongly (p = 0.003 and 0.001, respectively), and BASDAI 1, 4, and 5 correlate moderately (p = 0.03, 0.02, and 0.01, respectively)], followed by stiffness, upper back pain, pain with pressure, lower back pain, fatigue, and joint pain. Stiffness correlated strongly with nine of ten items on BASFI (BASFI 1 showed moderate correlation, p = 0.01), followed by upper back pain (four of ten items correlated strongly, three of ten correlated moderately), neck pain (three of ten tasks correlated strongly and four of ten correlated moderately), lower back pain (one task correlated strongly, five moderately), joint pain and swelling (four tasks correlated moderately), fatigue (three tasks correlated moderately), and pain with pressure (two tasks correlated moderately). BASDAI and BASFI only partly reflect disease activity and patients’ functional capacity in SpAs. An alternate instrument is required to assess SpA disease activity and functional capacity more precisely.