What does adolescent undiagnosed wheeze represent? Findings from the Isle of Wight Cohort

We sought to characterise adolescent wheeze in the absence of asthma, which we termed "undiagnosed wheeze". The Isle of Wight Birth Cohort (n=1,456) was reviewed at 1, 2, 4, 10 and 18 yrs. Using questionnaire responses, "asthma" was defined as "ever had asthma" plus either "wheezing in the last 12 months" or "taking asthma treatment in the last 12 months"; "undiagnosed wheeze" as "wheeze in the last 12 months" but "no" to "ever had asthma"; and remaining subjects termed "non-wheezers". Undiagnosed wheeze (prevalence 4.9%) accounted for 22% of wheezing at 18 yrs. This was largely adolescent-onset with similar symptom frequency and severity to diagnosed asthma. However, undiagnosed wheezers had significantly higher forced expiratory volume in 1 s to forced vital capacity ratio, less bronchodilator reversibility and bronchial hyperresponsiveness, and were less frequently atopic than asthmatics. Undiagnosed wheezers had earlier smoking onset, higher smoking rates and monthly paracetamol use than non-wheezers. Logistic regression identified paracetamol use (OR 1.11, 95% CI 1.01-1.23; p=0.03), smoking at 18 yrs (OR 2.54, 95% CI 1.19-5.41; p=0.02), rhinitis at 18 yrs (OR 2.82, 95% CI 1.38-5.73; p=0.004) and asthmatic family history (OR 2.26, 95% CI 1.10-4.63; p=0.03) as significant independent risk factors for undiagnosed wheeze. Undiagnosed wheeze is relatively common during adolescence, differs from diagnosed asthma and has strong associations with smoking and paracetamol use. Better recognition of undiagnosed wheeze and assessment of potential relevance to adult health is warranted.     

Dihydropyrimidinones: efficient one-pot green synthesis using Montmorillonite-KSF and evaluation of their cytotoxic activity

A simple, efficient, cost-effective, recyclable and green approach has been developed for the synthesis of new dihydropyrimidinone analogs via the Biginelli reaction. The methodology involves a multicomponent reaction catalyzed by “HPA-Montmorillonite-KSF” as a reusable and heterogeneous catalyst. This method gives an efficient and much improved modification of the original Biginelli reaction, in terms of yield and short reaction times under solvent free conditions. All the derivatives were subjected to cytotoxicity screening against a panel of four different human cancer cell lines viz. colon (Colo-205), prostate (PC-3), leukemia (THP-1) and lung (A549) to check their effect on percentage growth. MTT [3-(4,5-dimethylthiazol-yl)-diphenyl tetrazoliumbromide] cytotoxicity assay was employed to check IC₅₀ values. Of the synthesized analogs, 16a showed the best activity with IC₅₀ of 7.1 ± 0.8, 13.1 ± 1.4, 13.8 ± 0.9 and 14.7 ± 1.1 μM against lung (A549), leukemia (THP-1), prostate (PC-3) and colon (Colo-205) cancer lines, respectively. The 16a analog was further checked for its effect on cancer cell properties through clonogenic (colony formation) and scratch motility (wound healing) assays and thereby was found that it reduced both the colony formation and migratory properties of the lung cancer cell line (A549). Further, molecular docking studies were performed with 16a to show its binding mode.

The general method for the preparation of DHPM analogs; cytotoxic activity and binding mode of the most active derivative against PI3Kγ and CDK2 targets.     

Breast metastases from undifferentiated nasopharyngeal carcinoma

The most common primary tumours metastasising to the breast include melanoma, lymphoma, lung cancer and ovarian cancer, while metastases from head and neck cancer are rare. Metastases from undifferentiated nasopharyngeal carcinoma cancers are extremely rare, and only 3 well-documented cases have been reported in the English literature. We report a fourth case of breast metastases from nasopharyngeal carcinoma confirmed by in situ hybridization, focusing on clinical data as well as radiologic and pathologic features.     

Effect of ENPP1/PC-1-K121Q and PPARgamma-Pro12Ala polymorphisms on the genetic susceptibility to T2D in the Tunisian population

Diabetes mellitus is the most common chronic metabolic disease. The raising diabetes epidemic is unfolding as an interaction between several environmental factors and a genetic predisposition. The aim of the current study was to evaluate the role of the PPARγ-Pro12Ala and ENPP1-K121Q polymorphisms on type 2 diabetes (T2D) risk in a case–control study in the Tunisian population. To assess for any association of ENPP1-K121Q and PPARγ-Pro12Ala polymorphisms with T2D risk, we analysed the genotypic and allelic distributions of each variant in the studied cohort. Our results support that the genetic variation at ENPP1-K121Q predisposes to T2D in the Tunisian population after adjustment on gender, age and BMI status (OR = 1.55, 95%CI [1.11–2.16], p = 0.007).Conversely, the PPARγ-Pro12Ala variant seems not to have a significant effect on T2D risk in our Tunisian cohort. However, the minor A-allele would convey protection against overweight in the Tunisian population. In fact, the over weighted subjects showed a significantly lower frequency of A-allele than lean controls (OR = 0.49, 95%CI [0.25–0.97], p = 0.02). In conclusion, our findings support the hypothesis that ENPP1-121Q is involved in the genetic susceptibility of T2D in the Tunisian population, while the PPARγ-12Ala allele may confer protection against overweight.     

Ectopic prolactinoma of the sphenoidal sinus: case report

A 34-year-old woman was hospitalized for exploration of amenorrhea and galactorrhea. She had experienced primary sterility, diagnosed 11 years earlier. Endocrine tests demonstrated hyperprolactinemia (serum prolactin 594 ng/ml). Magnetic resonance imaging (MRI) showed a soft tissue mass located within the posterior part of the sphenoidal sinus. The pituitary gland appeared normal. Medical treatment with bromocriptine was unsuccessful. Transsphenoidal tumor resection was performed. Histology reported adenoma, which was consistent with prolactin-producing tumor demonstrated by immunohistochemical staining for prolactin. Because of the persistence of hyperprolactinemia related to an intra-sphenoidal tumor remnant, bromocriptine (15 mg/d) was initiated. Menses ensued and prolactin level declined (49 ng/ml). One year later, the tumor remnant had disappeared on the MRI and the patient became pregnant. Ectopic adenomas of the sphenoidal sinus are of particular interest due to the diagnostic difficulties encountered. Nevertheless, the nature of the lesion can be determined from the endocrine manifestations. Some of these tumors respond to medical treatment, similar to intra sellar tumors. Surgery remains however the only means of obtaining definitive diagnosis and cure.