Association of mutations in FLNA with craniosynostosis

Mutations of FLNA, an X-linked gene that encodes the cytoskeletal protein filamin A, cause diverse and distinct phenotypes including periventricular nodular heterotopia and otopalatodigital spectrum disorders (OPDS). Craniofacial abnormalities associated with OPDS include supraorbital hyperostosis, down-slanting palpebral fissures and micrognathia; craniosynostosis was previously described in association with FLNA mutations in two individual case reports. Here we present four further OPDS subjects who have pathological FLNA variants and craniosynostosis, supporting a causal link. Together with the previously reported patients, frontometaphyseal dysplasia was the most common clinical diagnosis (four of six cases overall); five patients had multiple suture synostosis with the sagittal suture being the most frequently involved (also five patients). No genotype–phenotype correlation was evident in the distribution of FLNA mutations. This report highlights the need to consider a filaminopathy in the differential diagnosis of craniosynostosis, especially in the presence of atypical cranial or skeletal features.     

Hypoglycaemic activity of commelina africana and ageratum conyzoides in relation to their mineral composition

Background

Many plants with antidiabetic properties probably act in part through their content of fibre, vitamins, bioactive or mineral content

Objectives

This study investigated the mineral, proximate, phytochemical compositions and hypoglycaemic effect of Commelina africana and Ageratum conyzoides extracts in diabetic rats, and the likely relationship between this property and the mineral, proximate and phytochemical compositions of the plants.

Methods

The plants were subjected to mineral, proximate composition and phytochemical analysis. Attempt was made to see (if any) the relationship between the hypoglycaemic effect and the mineral, proximate compositions and phytochemistry of the plants. Alloxan-induced diabetic animals were administered 500mg/kg body weight aqueous extracts of the plants and glibenclamide as the reference hypoglycaemic agent.

Results

Aqueous extract of Ageratum conyzoides reduced fasting blood glucose of experimental animals by 39.1% while Commelina africana reduced the same by 78.0%. Alkaloids, cardenolides, saponins, and tannins were detected in both plants. Anthraquinones was absent in C. africana but a trace of it was detected in A. conyzoides. The hypoglycaemic effect of Commelina africana was comparable with the reference hypoglycaemic agent. Ageratum conyzoides showed comparably weaker hypoglycaemic effect than exhibited by reference hypoglycaemic agent. Comparatively, Commelina africana had higher mineral concentrations (except Na) than Ageratum conyzoides.

Conclusions

Plants'' extracts minerals (magnesium, potassium and iron) and bioactive components (alkaloids and cardenolides) seemingly enhanced their hypoglycaemic effect. Furthermore, these minerals, alkaloids and cardenolides could be helpful in ameliorating complications of diabetes like hypertension and cardiovascular disease.     

Upper GI bleeding among neonates admitted to Mulago Hospital,Kampala, Uganda: a prospective cohort study

Background

The World Health Organization (WHO) reports estimate that 85% of newborn deaths are due to infections, prematurity and fetal distress. These conditions are risk factors for upper GI bleeding (UGIB) in sick neonates. UGIB is associated with poor neonatal outcomes such as prolonged hospitalisation and poor weight gain. The magnitude of UGIB and its contribution to neonatal morbidity has not been described in most low income countries.

Objective

To determine the occurrence and factors associated with UGIB among neonates admitted to the Special Care Unit (SCU) of Mulago Hospital.

Methods

This was a prospective single cohort study where neonates admitted within 24 hours of birth were consecutively enrolled and followed up for seven days. Gastric aspirates from the neonates were examined daily over a period of 7 days using Guaiac and Apt tests for evidence of UGIB. Data on occurrence of UGIB has been presented as proportions and Odds Ratios for associated factors.

Results

Out of 191 neonates, 44 (23 %) developed UGIB. Factors independently associated with UGIB included cyanosis in the neonate [OR 5.8; (95% CI; 1.8 – 19.1) p-value 0.004], neonatal seizures [OR 12.6; (95% CI 2.3 – 70.5); p-value 0.004] and birth asphyxia [OR 6.3; (95% CI 1.9 – 21.6); p-value 0.003].

Conclusions

In the first seven days of life, UGIB occurred in 1:4 neonates. Factors independently associated with UGIB included birth asphyxia, cyanosis in the neonate and neonatal seizures.     

Localization of the G-CSF gene on chromosome 17 proximal to the breakpoint in the t(15;17) in acute promyelocytic leukemia

The human granulocyte-colony stimulating factor gene (G-CSF) is localized at 17q11.2-q21, the region of one of the breakpoints in the 15;17 chromosome translocation specific for acute promyelocytic leukemia (APL). As G-CSF induces differentiation and loss of tumorigenicity in myeloid leukemic cells or cell lines, it was possible that the translocation in APL involved the DNA of the G-CSF coding region or its regulatory region. In situ hybridization to chromosomes with the t(15;17) from patients with the APL translocation using a G- CSF cDNA clone revealed that the coding region of this gene is proximal to the t(15;17) breakpoint on chromosome 17. Southern analysis of DNA from patients with the APL translocation showed no differences in hybridization between normal and leukemic cells. These results indicate that the G-CSF coding sequence is not disrupted by the chromosomal rearrangement characteristic of APL.