Periodontitis & sub-fertility; opinions and practices of Nigerian specialists.

BACKGROUND: Increasing evidence in the emerging field of periodontal medicine continues to stimulate research to verify the association between chronic periodontitis and general health. The link between chronic periodontitis and sub-fertility has not been well-investigated except for a handful of reports spanned over several decades. METHODS: As a prelude to a series of observational and interventional studies, 119 specialists and doctors participated in an online survey to ascertain their practices and opinions about this link. Our main exposure variables were dental history taking, periodontal/dental referrals and knowledge of possible link between chronic periodontitis and sub-fertility. RESULTS/FINDINGS: Our findings showed that dental history taking and periodontal/dental referrals were not part of sub-fertility management protocols of Nigerian specialists and doctors. These findings proved true irrespective of basic and postgraduate experience. Specialty was the only explanatory variable that accounted for statistical significance with the main exposure variables but the figures of members of different specialties were too low for any meaningful comparisons. CONCLUSIONS: The findings confirmed our suspicion of an almost complete lack of knowledge of this unlikely yet plausible association which deserves further research.

Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours.

BACKGROUND: Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, enhanced the efficacy of chemotherapy in human xenograft tumour models. This phase I study investigated the safety, tolerability, pharmacokinetics and antitumour activity of axitinib combined with chemotherapy. METHODS: A total of 42 patients with advanced solid tumours received a continuous axitinib starting dose of 5 mg twice daily (b.i.d.) plus paclitaxel (90 mg m(-2) weekly), docetaxel (100 mg m(-2) every 3 weeks) or capecitabine (1000 or 1250 mg m(-2) b.i.d., days 1-14). RESULTS: Common treatment-related adverse events across all cohorts were nausea (45.2%), hypertension (45.2%), fatigue (42.9%), diarrhoea (38.1%), decreased appetite (33.3%) and hand-foot syndrome (31.0%). There was one complete response, nine partial responses and seven patients with stable disease. Ten patients (23.8%) remained on therapy for >8 months. Paclitaxel and capecitabine pharmacokinetics were similar in the absence or presence of axitinib, but docetaxel exposure was increased in the presence of axitinib. Axitinib pharmacokinetics were similar in the absence or presence of co-administered agents. CONCLUSIONS: Axitinib combined with paclitaxel or capecitabine was well tolerated; no additive increase in toxicities was observed. Antitumour activity was observed for each treatment regimen and across multiple tumour types.

Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours.

BACKGROUND: This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours. METHODS: In all, 49 patients received axitinib 5 mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5 mg b.i.d. with paclitaxel/carboplatin. RESULTS: Two patients experienced dose-limiting toxicities: febrile neutropenia (n=1) in the paclitaxel/carboplatin cohort and fatigue (n=1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No grade ≥3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n=27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n=21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination. CONCLUSION: Axitinib 5 mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug-drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.

A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy.

PURPOSE: Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. METHODS: Women who received adjuvant chemotherapy 1-5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. RESULTS: Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory-the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p = 0.033) and HVLT-R Discrimination (p = 0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. CONCLUSION: Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. IMPLICATIONS FOR CANCER SURVIVORS: Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results.

Protective role of the methanolic extract of Icacina trichantha on sodium arsenite induced genotoxicity and hepatotoxicity.

BACKGROUND: Arsenic is a toxic metalloid, whose toxicity has raised a lot of concern. Humans are exposed to this metalloid through contaminated water, air and even foods. As a sulfhydryl reactive metal, arsenic has been found to cause extensive damage to organs such as the liver. It has also been found to be a potent clastogen, causing DNA damage leading to both benign and malignant tumors. OBJECTIVES: The anti-hepatotoxic and anti-genotoxic effects of methanolic leaf extract of Icacina trichantha on sodium arsenite induced toxicity in rats were determined. METHODS: Oral gavage of sodium arsenite was used to induced genotoxicity in rats and micronucleus assay was used to measure the number of micronucleated polychromatophilic erythrocytes. The determination of activities of serum alanine amino transferase (ALT), aspartate amino transferase (AST) and gamma glutamyl transferase (GGT) activities were used for the hepatotoxicity assay.. RESULTS: The mean number of micronucleated polychromatophilic erythrocytes (MPCE) per 1000 cells +/- SEM from the bone marrow smear was 57.50 +/- 9.71 in rats treated with both arsenite and extract compared to 129.00 +/- 16.34 in rats treated with arsenite alone. The serum ALT, AST and GGT activities +/- SEM were 67.04 + 3.71, 39.12 +/- 3.45 and 11.54 +/- 0.42 lu respectively for the rats treated with arsenite alone. Combined treatment of arsenite and the extract significantly decrease (p<0.05) in the activity of the enzymes, 29.75 +/- 3.43, 15.8 +/- 4.42, 6.87 +/- 0.433 lu for serum ALT, AST and GGT respectively. CONCLUSION: The methanolic leaf extract of I. trichantha modulated both the hepatotoxic and genotoxic effect induced by sodium arsenite in rats, which suggest that Icacina trichantha may serve as a hepatoprotective and anti-tumor agent.

Effects of herbal remedies (Agyanom mixture, Bolex bitters and Remedia mixture) on hepatic and renal functions in male rats.

BACKGROUND: Many people use herbal remedies for the treatment of a wide range of diseases due to the claims of their efficacies by the manufacturers. However, there is little insight as to the mode of action and possible toxic effects of these popular herbal formulations on organs such as, liver and kidney. OBJECTIVE: Hepatological, histological and renal function tests of Sprague-Dawley albino rats were investigated in order to determine the possible effects on rat kidney and liver following exposure of the physiological system to the processed herbal remedies through oral administration. METHODS: Thirty male Sprague-Dawley rats (120-170g) and divided into 7 groups were employed for this study. Six groups of 4 rats each were orally administered high dose (1.0 ml) and low dose (0.5 ml) of 'Agyanom mixture', 'Bolex bitters' and 'Remedia mixture' respectively for 15 days. The control group consisted of 6 rats given water only after acclimatization for 28 days, with food and water freely available to both groups. The rats were sacrificed, the blood samples were collected through the orbital sinus and cardiac puncture. The liver and kidney tissues for each group were also harvested. Liver and renal function test parameters were analysed. The liver and kidney from the rats were fixed in 10% formol saline and after 72 hours, dehydrated in graded alcohol, cleaned in xylene, and embedded in paraffin. The resulting blocks were sectioned. The sections were randomized and selected sections were stained in haemotoxylin and eosin. The slides were then examined at magnification of x400. RESULTS: There were significant (p < 0.05) differences in the concentrations of serum electrolytes in all the experimental groups compared with control. Na+, K+, HCO3(2-) urea and creatinin levels increased significantly in the experimental groups. Serum alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase activities and bilirubin level were not significantly different (p > or = 0.05) in all the experimental groups compared with control. Histological features of mild to severe tubular necrosis were evident in the kidney tissues of all the experimental groups compared to the control, unlike in the liver tissues. CONCLUSION: Data of the present study indicate that herbal remedies such as 'agyanom mixture', 'bolex bitters' and 'remedia mixture' have adverse effects on the kidney and they might not be safe for human consumption.