Obstetric and neonatal outcomes associated with maternal naltrexone exposure

Poor maternal and neonatal outcomes are associated with the pregnant heroin user. These include increased antepartum haemorrhage, decreased neonatal birthweight and increased neonatal mortality Medically supervised withdrawal from heroin during pregnancy has, however, been discouraged due to possible risk to the fetus and because of the high incidence of return to regular illicit heroin use by the mother. In recent years, however, a number of withdrawal procedures using anaesthesia, oral sedation, or intravenous sedation, precipitated by naloxone and/or naltrexone have been developed and carried out successfully on pregnant heroin users. We have now collated information on 18 cases (19 detoxifications) from three countries (Portugal, Australia and the United Kingdom). These case study data, although limited, indicate that detoxification of the pregnant heroin user is possible without significant risk to the neonate or mother, with many women not returning to dependent heroin use following detoxification. Naltrexone maintenance has also been used in the non-pregnant heroin user to discourage illicit heroin use. Similarly to methadone, stabilisation on naltrexone may be associated with conception and pregnancy Over the past three years, 26 women have conceived while on the Western Australia naltrexone program. Due to the unknown teratogenic effects, most have ceased naltrexone intake at approximately seven or eight weeks gestation. In a number of instances, however, naltrexone maintenance has been recommenced following return to a dependent pattern of heroin use. As a consequence, neonates have had different periods of naltrexone exposure, building from the initial seven or eight weeks. We now report on seven women who have delivered and three who are well into their third trimester. Neonatal and obstetric features were unremarkable with good Apgar scores, birthweight and head circumference observed. In the three cases still in third-term gestation, normal fetal development has been observed at recent ultrasound examinations. These case data indicate that naltrexone maintenance may have a role in the management of the pregnant heroin user.     

Anti-Inflammatory and Antioxidant Effects of an Ethanolic Extract of the Aerial Parts of Hilleria Latifolia (Lam.) H. Walt. (Phytolaccaceae)

Various parts of the perennial herb Hilleria latifolia (Lam.) H. Walt. (Family: Phytolaccaceae) are used in Ghanaian traditional medicine for the treatment of several inflammatory-related disorders. The present study examined the anti-inflammatory effect of an ethanolic extract of the aerial parts of Hilleria latifolia (HLE) in acute and chronic inflammation models. Since free radicals and reactive oxygen species are implicated in inflammatory diseases, the antioxidant potential of HLE was also investigated in in vitro experimental models. HLE (10–300 mg kg⁻¹, p.o.), either preemptively or curatively, significantly inhibited carrageenan-induced foot oedema in 7-day old chicks. Similarly, the NSAID diclofenac (10–100 mg kg⁻¹, i.p.) and the steroidal anti-inflammatory agent dexamethasone (0.3–3 mg kg⁻¹, i.p.) dose-dependently reduced the oedema in both pre-emptive and curative treatments. In the Freund''s adjuvant induced-arthritis model in rats, HLE as well as the positive controls, dexamethasone and methotrexate, showed significant anti-arthritic properties when applied to established adjuvant arthritis. HLE (10–300 mg kg⁻¹, p.o.) significantly reduced oedema in the ipsilateral paw of rats but failed to prevent systemic arthritic spread. The DMARD methotrexate (0.1–1 mg kg⁻¹, i.p.) and dexamethasone (0.3–3 mg kg⁻¹, i.p.) reduced significantly the total polyarthritic oedema as well as the spread of the arthritis from the ipsilateral to the contralateral paws of the treated animals. The extract (0.03–1.00 mg ml⁻¹) exhibited Fe³⁺ reducing activity, scavenged DPPH and prevented lipid peroxidation. These findings suggest that the extract exerts in vivo anti-inflammatory activity after oral administration and also has antioxidant properties which may contribute to its activity.     

Linkage analysis of candidate regions for coeliac disease genes

A strong HLA association is seen in coeliac disease [specifically to the DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. One or more genes at HLA-unlinked loci also predispose to coeliac disease and are probably stronger determinants of disease susceptibility than HLA. A recent study has proposed a number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked susceptibility gene. We have examined these regions in 28 coeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus telomeric to HLA. No significant evidence in favour of linkage to coeliac disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing close to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chromosome 15q26 is not strong, the well established association between coeliac disease and insulin dependent diabetes mellitus, together with the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring susceptibility to coeliac disease in some families.      

Cognitive screening tools for primary care settings: examining the ‘Test Your Memory’ and ‘General Practitioner assessment of Cognition’ tools in a rural aging population in Greece

Background: Under conditions of high demand for primary care services in a setting of low financial resources, there is need for brief, easily administered cognitive screening tools for use in the primary care setting, especially in rural areas. However, interpretation of these cognitive tests’ results requires knowledge on their susceptibility to cultural, educational and demographic patient characteristics.

Objectives: To assess the clinical validity of the ‘Test Your Memory’ (TYM) and ‘General Practitioner assessment of Cognition’ (GPCog) which was specifically designed for primary care practice, in a rural primary care setting in Greece, utilizing the ‘Mini Mental State Examination’ (MMSE) as a reference standard.

Methods: The MMSE, TYM, and GPCog were administered to a random sample of 319 community dwelling Greek adults aged 60 to 89 years in 11 rural Primary Healthcare Centres of the Prefecture of Heraklion on the island of Crete, Greece. Analyses examined (a) The association of each instrument with demographic factors and MMSE and (b) optimal cut-off scores, sensitivity and specificity against MMSE-based cognitive impairment risk using ROC analyses with the MMSE 23/24 point cut-off as a reference standard.

Results: We found a sensitivity of 80% and a specificity of 77% for TYM (35/36 or 38/39 cut-off, depending on education). Corresponding values were 89% and 61% for GPCog (7/8 cut-off), respectively.

Conclusion: The TYM and GPCog instruments appear to be suitable for routine use in the primary care setting as tools for cognitive impairment risk detection in elderly rural populations.     

Evidence for a multistep pathogenesis of chronic myelogenous leukemia

To study the relationship of the Philadelphia chromosome (Ph1) to the pathogenesis of chronic myelogenous leukemia, multiple B-lymphoid cell lines were established from a patient with Ph1-positive leukemia who was heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase. Both A and B types of enzyme were found in a 1:1 proportion in normal tissues, but 45 of 63 (71%) Ph1-negative B- lymphoid cells lines derived from this patient showed only the single glucose-6-phosphate dehydrogenase (type B) found in the Ph1-positive leukemic clone. Furthermore, 8 of 33 analyzable lines with B-type enzyme had chromosomal aberrations compared to 0 of 14 lines with A- type glucose-6-phosphate dehydrogenase. These results provide evidence for the suggestion that some cells of the abnormal clone do not express the Ph1 abnormality. Thus, acquisition of Ph1 may not be a sufficient cause for the disease. It is possible that at least two steps are involved in the pathogenesis of Ph1-positive chronic myelogenous leukemia, one causing abnormal proliferation of a clone of pluripotent hematopoietic stem cells and the other inducing Ph1 in descendants of these progenitors.