An individual scoring system for the prediction of postpartum anaemia

Background

Postpartum anaemia (PPA) is a common postpartum complication. The goal of this study was to prospectively construct a predictive score for individual risk of PPA.

Patients et method

We prospectively analyzed factors associated with PPA (< 10 g dL⁻¹ at 48 hours postpartum). Parameters analyzed were demographic data, pregnancy characteristics, delivery and postpartum characteristics. Univariate analysis was performed using Anova or X²; the Cox model was used for multivariate analysis. The scoring system was validated using ROC curve.

Results

Analysis was performed in 475 patients and validation was carried using an additional 95 patients. Multivariate analysis found four factors independently associated with PPA: anaemia during the third trimester of the pregnancy, Southeast Asian ethnic origin, episiotomy and severe postpartum haemorrhage (PPH) identified by the use of sulprostone. According to the score derived from the Cox model, patients were classified as low (22%, score = 0), medium (55%, score = 2 or 3) and high (86%, score > 3) probability of PPA. Using the AUC of the ROC curve for both the first and the validation cohorts (performed on 95 further patients), we recorded AUCs of 72% and 70% respectively.

Conclusions

This study allowed the derivation and validation of a predictive score of PPA. This score might be useful in targeting prophylactic strategies for PPA. Such strategies could include a more active treatment of iron deficiency (increasing oral iron treatment observance or intravenous iron therapy) especially in exposed population, improvement in the prevention and treatment of postpartum haemorrhage and decreasing the use of episiotomy. Future studies must focus on the external validation and generalisation of this scoring system.     

School health promotion in South‐East Asia by Japan and partners

School health promotion in South‐East Asia has developed rapidly in recent years, and Japan has been one of the significant contributors to the reinforcement of school health promotion in the region. Starting from the Hashimoto Initiative on global parasite control, Japan advocated for international partnerships with several agencies for the development of school health programs in South‐East Asia. Through a strengthened collaboration with international organizations, countries such as the Lao PDR, Cambodia, the Philippines, and Thailand have created and implemented school health programs on nutrition, sanitation, and deworming, among others. In addition to school health program formulation and implementation, the expanded network in South‐East Asia led to more capable school health personnel, with many workers in the education and health sectors benefitting from the training programs jointly held by collaborating organizations.     

Hypoglycaemia in type 1 diabetes: technological treatments,their limitations and the place of psychology

Advances in technology allowing improved insulin delivery and glucose monitoring can significantly reduce the burden of hypoglycaemia when used appropriately. However, limitations of the current technology, and the skills, commitment and motivation required to use them, mean that it does not work for all people. Education and informed professional support are key to success. In the context of problematic hypoglycaemia, data suggest that newer technology has lower efficacy and uptake in those with most need. Identifying the causes of hypoglycaemia and understanding some of the underlying behavioural drivers may prove useful and psycho-educational strategies may be effective in selected individuals. Ultimately, as in many spheres of medicine, successful management of problematic hypoglycaemia depends upon matching the right treatment to the right individual.     

Novel method for the quantitative assessment of cell migration: a study on the motility of rabbit anterior cruciate (ACL) and medial collateral ligament (MCL) cells

A novel method of quantitating cell migration has been proposed for the potential utilization of tissue engineered scaffolds. Applying Alt's conservation law to describe the motion of first passage ACL and MCL cells, we have developed a quantitative method to assess innate differences in the motility of cells from these two ligamentous tissues. In this study, first passage ACL and MCL cells were cultured from four mature New Zealand white rabbits. One side of the cell monolayer was scraped completely away to create a wound model. The cell moved into the cell-free area, and cell density profiles were analyzed at 6 h and 12 h. Values of the random motility coefficient (mu) were then estimated by curve fitting the 6 h and 12 h data to a mathematical model, derived from the conservation law of cell flux. During 6 h of incubation in medium supplemented with 1% FBS, MCL cells (mu(MCL) = 4.63 +/- 0.65 X 10(-6) mm(2)/sec) were significantly (p < 0.05) more mobile than ACL cells (mu(ACL) = 2.51 +/- 0.31 X 10(-6) mm(2)/sec). At 12 h, the MCL cells also appeared to move faster (mu(ACL) = 4.39 +/- 0.63 X 10(-6) mm(2)/sec, mu(MCL) = 6.59 +/- 1.47 X 10(-6) mm(2)/sec), but the difference was not statistically significant (p = 0.18). Exposure of the cells to growth factors PDGF-BB or bFGF for 6 h had no significant effect on the migration of the ACL and MCL cells. However, exposure of the ACL cells (p < 0.05) and the MCL cells (p = 0.19) to 1 ng/mL of PDGFBB for 12 h enhanced their migration. Incubation with a high concentration (100 ng/mL) of PDGF-BB or bFGF at concentrations tested (1 or 100 ng/mL) for 12 h, produced little or no migratory stimulation on these ligament cells. Our findings support the previous qualitative observations made by numerous investigators. The novel methodology developed in this study may provide a basis for tissue engineering, and the results may be applied to tissue reconstruction techniques of the knee ligaments.     

Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders

Background

Autism spectrum disorders (ASD) refer to a broader group of neurobiological conditions, pervasive developmental disorders. They are characterised by a symptomatic triad associated with qualitative changes in social interactions, defect in communication abilities, and repetitive and stereotyped interests and activities. ASD is prevalent in 1 to 3 per 1000 people. Despite several arguments for a strong genetic contribution, the molecular basis of a most cases remains unexplained. About 5% of patients with autism have a chromosome abnormality visible with cytogenetic methods. The most frequent are 15q11–q13 duplication, 2q37 and 22q13.3 deletions. Many other chromosomal imbalances have been described. However, most of them remain undetectable using routine karyotype analysis, thus impeding diagnosis and genetic counselling.

Methods and results

29 patients presenting with syndromic ASD were investigated using a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Eight clinically relevant rearrangements were identified in 8 (27.5%) patients: six deletions and two duplications. Altered segments ranged in size from 1.4 to 16 Mb (2–19 clones). No recurrent abnormality was identified.

Conclusion

These results clearly show that array comparative genomic hybridisation should be considered to be an essential aspect of the genetic analysis of patients with syndromic ASD. Moreover, besides their importance for diagnosis and genetic counselling, they may allow the delineation of new contiguous gene syndromes associated with ASD. Finally, the detailed molecular analysis of the rearranged regions may pave the way for the identification of new ASD genes.Autism spectrum disorders (ASD) belong to the group of pervasive developmental disorders (PDD). According to the Diagnostic statistical manual for mental disorders—fourth edition (DSM IV) classification,¹ ASD are characterised by impairments in communication, social skills and restricted or stereotyped pattern of behaviours and interests. A diagnosis within the autism spectrum requires one or more symptoms in each of the three areas of impairment. The prevalence of ASD is estimated at about 1/1000 to 3/1000.^2,3 ASD are heterogeneous conditions which can be either isolated or syndromic—that is, associated with other clinical features such as facial dysmorphism, limb or visceral malformations, and growth abnormalities.A total of 10–20% of ASD cases are due to known medical conditions involving chromosomal imbalances, genetic disorders (X fragile syndrome and tuberous sclerosis)⁴ or environmental factors (valproate⁵ and rubella). The other cases remain unexplained. Twin and familial studies have documented a higher concordance rate in monozygotic twins (90%) than in dizygotic twins (4.5%),^6,7,8 and a 75‐fold greater risk to siblings in idiopathic patients than in the general population.^9,10 Collectively, these studies support the involvement of numerous genes in autistic disorders.About 1.7–4.8% of people with ASD have chromosome abnormalities. Almost all chromosomes have been involved, including unbalanced translocations, inversions, rings, and interstitial or terminal deletions and duplications.^11,12,13,14 The rare chromosome abnormalities that have been reported on more than one occasion are duplication of 15q,¹⁵ deletions of 18q,^16,17 Xp,^18,19 2q37,²⁰ 22q13^21,22 and the sex chromosome aneuploidies 47,XYY^23,24 and 45,X/46,XY.^25,26 This diversity of loci suggests that studying chromosomal aberrations in relationship to autism will require efficient and highly sensitive tools. In addition to the importance for diagnosis, identification of chromosomal imbalances in patients with ASD may also be instrumental for cloning disease‐causing genes. Analysis of Xp22.3 deletion has indeed allowed the identification of the NLGN4 gene.²⁷Recent technological developments, such as array‐based comparative genomic hybridisation (array‐CGH),^28,29,30 allow the investigation of the human genome at a resolution that is 5–10 times higher than that of routine chromosome analysis by karyotyping.^29,31,32,33 Array‐CGH has been used successfully for analysis of tumour samples and cell lines, and for high‐resolution analysis of patients with mental retardation and congenital anomalies.^{34,35,36,37,38}Here, we report the application of genomewide array‐CGH, at 1 Mb resolution, to the study of 29 patients with syndromic ASD. In addition to their clinical relevance, our results emphasise the importance of chromosomal imbalance in the aetiology of syndromic ASD and may help the identification of new genes involved in autistic disorders.     

Prostatic involvement by transitional cell carcinoma in patients with bladder cancer and its prognostic significance

To study the importance of prostatic involvement by transitional cell carcinoma (TCC) in patients with bladder cancer, we examined the entire prostates by whole-mount sections from 214 radical cystoprostatectomy specimens for detailed patterns of involvement by TCC and correlated the results with lymph node metastasis and patients' survival. Prostatic involvement by TCC was detected in 69 (32%) of 214 cases. Among them, 30 (43%) patients had carcinoma in situ (CIS) and the other 39 (57%) were invasive TCC. Carcinoma in situ occurred in either prostatic urethra (n = 6, 20%) or, more commonly, in prostatic ducts/acini (n = 14, 47%), and in a combination of prostatic urethra and ducts (n = 10, 33%). Ten (26%) of the invasive TCC resulted from direct penetration from the primary tumor in the bladder, and the remaining 29 (72%) cases arose from prostatic urethra/ducts, of which 11, 13, and 5 invaded the lamina propria, prostatic stroma, and periprostatic or seminal vesical tissue, respectively. Both prostatic TCC involvement and nodal metastasis were highly significant prognostic factors for patients' survival and the survival significance of prostatic TCC involvement still existed regardless of lymph node status. Furthermore, the presence of prostatic CIS and degrees of prostatic invasion are associated with nodal metastasis and survival. Patients with prostatic CIS or urethral lamina propria invasion had a similar, but higher incidence of lymph node metastasis and lower long-term and 5-year survival than those patients without prostatic involvement. Similarly, prostatic stromal invasion and periprostatic/seminal vesical invasion had a similar, but much higher nodal metastasis and worse survival than patients with only prostatic CIS or urethral lamina propria invasion. In summary, presence of prostatic TCC involvement and levels of involvement are significant prognostic factors in patients with bladder cancer.     

Noradrenergic neuronal development is impaired by mutation of the proneural HASH-1 gene in congenital central hypoventilation syndrome (Ondine's curse)

Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is a rare disorder of the chemical control of breathing. It is frequently associated with a broad spectrum of dysautonomic symptoms, suggesting the involvement of genes widely expressed in the autonomic nervous system. In particular, the HASH-1-PHOX2A-PHOX2B developmental cascade was proposed as a candidate pathway because it controls the development of neurons with a definitive or transient noradrenergic phenotype, upstream from the RET receptor tyrosine kinase and tyrosine hydroxylase. We recently showed that PHOX2B is the major CCHS locus, whose mutation accounts for 60% of cases. We also studied the proneural HASH-1 gene and identified a heterozygous nucleotide substitution in three CCHS patients. To analyze the functional consequences of HASH-1 mutations, we developed an in vitro model of noradrenergic differentiation in neuronal progenitors derived from the mouse vagal neural crest, reproducing in vitro the HASH-PHOX-RET pathway. All HASH-1 mutant alleles impaired noradrenergic neuronal development, when overexpressed from adenoviral constructs. Thus, HASH-1 mutations may contribute to the CCHS phenotype in rare cases, consistent with the view that the abnormal chemical control of breathing observed in CCHS patients is due to the impairment of noradrenergic neurons during early steps of brainstem development.