Newcastle upon Tyne, United Kingdom
Newcastle upon Tyne, United Kingdom

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Sayers J.,Newcastle University | Hynes A.M.,Newcastle University | Srivastava S.,Newcastle University | Dowen F.,Newcastle upon Tyne NHS Hospitals Foundation Trust | And 6 more authors.
Clinical Kidney Journal | Year: 2015

Mutations in CYP24A1, encoding the vitamin D 24-hydroxlase enzyme, are known to cause a range of clinical phenotypes and presentations including idiopathic infantile hypercalcaemia and adult-onset nephrocalcinosis and nephrolithiasis. In the context of raised or borderline high serum calcium levels, suppressed PTH and persistently elevated 1,25 dihydroxy vitamin D levels, this rare condition should be considered.We present a case where this biochemical pattern was seen and mutations in CYP24A1 were confirmed. We were able to successfully control serum calcium levels and reduce urinary calcium excretion by treatment with low-dose fluconazole, which inhibits vitamin D-synthesizing enzymes (including 25-hydroxylases and 1-a- hydroxylase) thereby reducing levels of 1,25-dihydroxy vitamin D. © The Author 2015.


Elliott S.L.,Northumbria University | Crawford C.,Northumbria University | Mulligan E.,Northumbria University | Summerfield G.,Queen Elizabeth Hospital | And 7 more authors.
British Journal of Haematology | Year: 2011

Defects in the DNA damage response pathway [e.g. del(17p)] are associated with drug-resistant B-cell chronic lymphocytic leukaemia (CLL). We previously demonstrated that over-expression of DNA-dependent protein kinase (DNA-PK) correlates with chemo-resistance and that inhibition of DNA-PK sensitizes CLL cells to chemotherapeutics. Here, we investigated expression of DNA-PK and other proteins that impact on drug resistance, and evaluated the effects of a DNA-PK inhibitor (NU7441) on mitoxantrone-induced cytotoxicity in CLL cells. NU7441 sensitized cells from 42/49 CLL samples to mitoxantrone, with sensitization ranging from 2- to 200-fold Co-culture of CLL cells in conditioned stromal medium increased chemoresistance but did not reduce sensitization by NU7441. Mitoxantrone treatment induced γH2AX foci and NU7441 increased their longevity (24 h). NU7441 prevented mitoxantrone-induced autophosphorylation of the DNA-PK catalytic subunit (DNA-PKcs) at Ser 2056, confirming that DNA-PK participates in repair of mitoxantrone-induced DNA damage. del(17p) cases were more resistant to mitoxantrone than del(13q) cases, but were resensitized (7-16 fold) by co-incubation with NU7441. Expression of DNA-PKcs, Ku80, P-glycoprotein and topoisomerase IIβ were significantly higher in del(17p) cases. PRKDC mRNA levels correlated with DNA-PKcs protein expression, which predicted shorter survival. These data confirm the potential of DNA-PK as a therapeutic target in poor prognosis CLL. © 2010 Blackwell Publishing Ltd.


Graham Y.N.H.,University of Sunderland | Graham Y.N.H.,Sunderland Royal Hospital | Mansour D.,Newcastle upon Tyne NHS Hospitals Foundation Trust | Small P.K.,Sunderland Royal Hospital | And 6 more authors.
Obesity Surgery | Year: 2016

Background: Over 80 % of bariatric surgical patients are women with obesity in their reproductive years. Obesity adversely affects fertility; the rapid weight loss following bariatric surgery can increase fecundity. Current guidelines recommend avoiding pregnancy for up to 24 months following surgery, but little is known about current contraceptive care of women who undergo bariatric surgery. Two surveys were undertaken with bariatric surgical and contraceptive practitioners in England to establish current contraceptive practices in both groups. Methods: Two anonymous on-line surveys were sent to all 382 members of the British Obesity and Metabolic Surgery Society (BOMSS) and an estimated 300 contraceptive practitioners in the North East of England. Results: The BOMSS survey elicited a response rate of 17 % (n = 65), mainly from bariatric surgeons (n = 24 (36 %)). Most respondents (97 %) acknowledged the need to educate patients, but contraceptive information was only provided by 7 % (n = 4) of respondents in bariatric surgical clinics. Less than half of respondents were confident discussing contraception, and the majority requested further training, guidance and communication with contraceptive practitioners. The majority of respondents to the contraceptive practitioner survey were general practitioners (28 %, n = 20). Three quarters of respondents reported little knowledge of bariatric surgery, and many reported not seeing women with obesity requiring contraception before (66 %, n = 45) or after surgery (71 %, n = 49). Conclusions: There is a need to increase knowledge levels of contraception within bariatric surgical teams and to understand why, despite increasing levels of bariatric surgery, women do not seem to be appearing for advice in contraceptive settings. © 2016, Springer Science+Business Media New York.


PubMed | Sunderland Royal Hospital, University of Sunderland and Newcastle upon Tyne NHS Hospitals Foundation Trust
Type: Journal Article | Journal: Obesity surgery | Year: 2016

Over 80% of bariatric surgical patients are women with obesity in their reproductive years. Obesity adversely affects fertility; the rapid weight loss following bariatric surgery can increase fecundity. Current guidelines recommend avoiding pregnancy for up to 24months following surgery, but little is known about current contraceptive care of women who undergo bariatric surgery. Two surveys were undertaken with bariatric surgical and contraceptive practitioners in England to establish current contraceptive practices in both groups.Two anonymous on-line surveys were sent to all 382 members of the British Obesity and Metabolic Surgery Society (BOMSS) and an estimated 300 contraceptive practitioners in the North East of England.The BOMSS survey elicited a response rate of 17% (n=65), mainly from bariatric surgeons (n=24 (36%)). Most respondents (97%) acknowledged the need to educate patients, but contraceptive information was only provided by 7% (n=4) of respondents in bariatric surgical clinics. Less than half of respondents were confident discussing contraception, and the majority requested further training, guidance and communication with contraceptive practitioners. The majority of respondents to the contraceptive practitioner survey were general practitioners (28%, n=20). Three quarters of respondents reported little knowledge of bariatric surgery, and many reported not seeing women with obesity requiring contraception before (66%, n=45) or after surgery (71%, n=49).There is a need to increase knowledge levels of contraception within bariatric surgical teams and to understand why, despite increasing levels of bariatric surgery, women do not seem to be appearing for advice in contraceptive settings.


PubMed | Northumbria University and Newcastle upon Tyne NHS Hospitals Foundation Trust
Type: Journal Article | Journal: Clinical kidney journal | Year: 2015

Mutations in CYP24A1, encoding the vitamin D 24-hydroxlase enzyme, are known to cause a range of clinical phenotypes and presentations including idiopathic infantile hypercalcaemia and adult-onset nephrocalcinosis and nephrolithiasis. In the context of raised or borderline high serum calcium levels, suppressed PTH and persistently elevated 1,25 dihydroxy vitamin D levels, this rare condition should be considered. We present a case where this biochemical pattern was seen and mutations in CYP24A1 were confirmed. We were able to successfully control serum calcium levels and reduce urinary calcium excretion by treatment with low-dose fluconazole, which inhibits vitamin D-synthesizing enzymes (including 25-hydroxylases and 1--hydroxylase) thereby reducing levels of 1,25-dihydroxy vitamin D.

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