Dopamine D(1) agonist activates temporal lobe structures in primates

Changes in the function of dopamine D(1)-influenced neuronal pathways may be important to the pathophysiology of several human diseases. We recently developed methods for averaging functional imaging data across nonhuman primate subjects; in this study, we apply this method for the first time to map brain responses to experimental dopamine agonists in vivo. Here we report the use of positron emission tomography (PET) in seven normal baboons to measure the regional cerebral blood flow (rCBF) responses produced by an acute dose of the dopamine D(1) full agonist SKF82958. The most significant rCBF increases were in bilateral temporal lobe, including amygdala and superior temporal sulcus (6-17%, P < 0.001). Blood flow decreased in thalamus, pallidum, and pons (4-7%, P = 0.001). Furthermore the rCBF responses were dose-dependent and had a half-life of approximately 30 min, similar to that reported for the drug's antiparkinsonian effects. Absolute whole-brain blood flow did not change, suggesting that these local changes in rCBF reflect neuronal rather than direct vascular effects of the agonist. The prominent temporal lobe response to a D(1) agonist supports and extends our recent observations that levodopa produces prominent amygdala activation both in humans and in other primates. We speculate that levodopa may exert its known effects on mood in humans through increased amygdala activity, mediated in part by D(1) receptors.     

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.     

Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia

The importance of banded chromosome analyses in predicting long-term outcome in acute lymphoblastic leukemia (ALL) was evaluated in this follow-up study of 329 patients from the Third International Workshop on Chromosomes in Leukemia. Patients were divided into ten groups according to pretreatment karyotype: no abnormalities, one of the following structural abnormalities [the Philadelphia chromosome, translocations involving 8q24,t(4;11), 14q+, 6q-] or, in the remaining cases, modal number [less than 46, 46, 47 to 50, greater than 50]. Achievement and duration of complete remission (CR) and survival differed among chromosome groups (P less than .0001). Karyotype was an independent prognostic factor for duration of first CR and survival, even when age, initial leukocyte count (WBC), French-American-British (FAB) type, and immunologic phenotype were considered. Among adults, prolonged remission and survival were uncommon in all chromosome groups. Only in the normal karyotype group was median survival even two years. Among children, striking differences in long-term remission and survival were seen depending upon karyotype. Children in the greater than 50 group did best, with 70% remaining in first CR for a median duration in excess of five years. Children in the 47-50, 6q-, and normal karyotype groups also had prolonged survivals. In contrast, certain translocations [t(9;22)(q34;q11), t(4;11)(q21;q14-23), t(8;14)(q24;q32)] identified children who had short survivals, even in the presence of favorable prognostic factors including a low WBC, L1 morphology, and non-T, non-B immunologic phenotype. We conclude that chromosome analysis is required at diagnosis in patients with ALL, and that children with these specific translocations should be managed as having high-risk ALL.