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Articles by G Lewis
Total Records ( 8 ) for G Lewis
  G. M Tozer , V. E Prise , G Lewis , S Xie , I Wilson and S. A. Hill
 

Purpose: The therapeutic potential of combining the prototype tumor vascular-disrupting agent combretastatin A-4 3-O-phosphate (CA-4-P) with systemic nitric oxide synthase (NOS) inhibition was investigated preclinically.

Experimental Design: Vascular response (uptake of 125I-labeled iodoantipyrine; laser Doppler flowmetry) and tumor response (histologic necrosis; cytotoxicity and growth delay) were determined.

Results: Inducible NOS selective inhibitors had no effect on blood flow in the P22 rat sarcoma. In contrast, the non–isoform-specific NOS inhibitor N-nitro- l-arginine (l-NNA; 1 and 10 mg/kg i.v. or chronic 0.1 or 0.3 mg/mL in drinking water) decreased the P22 blood flow rate selectively down to 36% of control at 1 hour but did not induce tumor necrosis at 24 hours. CA-4-P, at clinically relevant doses, decreased the P22 blood flow rate down to 6% of control at 1 hour for 3 mg/kg but with no necrosis induction. However, l-NNA administration enhanced both CA-4-P–induced tumor vascular resistance at 1 hour (chronic l-NNA administration) and necrosis at 24 hours, with 45% or 80% necrosis for 3 and 10 mg/kg CA-4-P, respectively. Bolus l-NNA given 3 hours after CA-4-P was the most effective cytotoxic schedule in the CaNT mouse mammary carcinoma, implicating a particular enhancement by l-NNA of the downstream consequences of CA-4-P treatment. Repeated dosing of l-NNA with CA-4-P produced enhanced growth delay over either treatment alone in P22, CaNT, and spontaneous T138 mouse mammary tumors, which represented a true therapeutic enhancement.

Conclusions: The combination of NOS inhibition with CA-4-P is a promising approach for targeting tumor vasculature, with relevance for similar vascular-disrupting agents in development.

  G Lewis and A. P. Maxwell
 

Erythropoiesis stimulating agents (ESAs) are used to mange anaemia secondary to chronic kidney disease (CKD). ESAs have also been used to augment the rate of iron loss by phlebotomy in some iron storage disorders. We report the use of erythropoietin to allow enhanced iron removal in a man with both hereditary haemochromatosis and CKD. The patient subsequently presented with more severe anaemia that prompted a search for an underlying occult malignancy. The case history illustrates the importance of considering alternative causes for anaemia in patients with CKD.

  K Thomas , G Harrison , S Zammit , G Lewis , J Horwood , J Heron , C Hollis , D Wolke , A Thompson and D. Gunnell
 

Background

Previous studies have suggested that impaired fetal and childhood growth are associated with an increased risk of schizophrenia, but the association of pre-adult growth with non-clinical psychotic symptoms (psychosis-like symptoms) in children is not known.

Aims

To explore the associations of body size at birth and age 7.5 years with childhood psychosis-like symptoms.

Method

Prospective cohort of children followed up from birth to age 12: the ALSPAC cohort.

Results

Data on 6000 singleton infants born after 37 weeks of gestation. A one standard deviation increase in birth weight was associated with an 18% reduction in the risk of definite psychosis-like symptoms after adjusting for age and gestation (Odds ratio (OR) = 0.82, 95% CI = 0.73–0.92, P = 0.001). This association was partly confounded by maternal anthropometry, smoking during pregnancy, socioeconomic status and IQ. A similar association was seen for birth length and psychosis-like symptoms, which disappeared after controlling for birth weight. There was little evidence for an association of 7-year height or adiposity with psychosis-like symptoms.

Conclusions

Measures of impaired fetal, but not childhood, growth are associated with an increased risk of psychosis-like symptoms in 12-year-olds.

  S Zammit , K Thomas , A Thompson , J Horwood , P Menezes , D Gunnell , C Hollis , D Wolke , G Lewis and G. Harrison
 

Background

Adverse effects of maternal substance use during pregnancy on fetal development may increase risk of psychopathology.

Aims

To examine whether maternal use of tobacco, cannabis or alcohol during pregnancy increases risk of offspring psychotic symptoms.

Method

A longitudinal study of 6356 adolescents, age 12, who completed a semi-structured interview for psychotic symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.

Results

Frequency of maternal tobacco use during pregnancy was associated with increased risk of suspected or definite psychotic symptoms (adjusted odds ratio 1.20, 95% CI 1.05–1.37, P = 0.007). Maternal alcohol use showed a non-linear association with psychotic symptoms, with this effect almost exclusively in the offspring of women drinking >21 units weekly. Maternal cannabis use was not associated with psychotic symptoms. Results for paternal smoking during pregnancy and maternal smoking post-pregnancy lend some support for a causal effect of tobacco exposure in utero on development of psychotic experiences.

Conclusions

These findings indicate that risk factors for development of non-clinical psychotic experiences may operate during early development. Future studies of how in utero exposure to tobacco affects cerebral development and function may lead to increased understanding of the pathogenesis of psychotic phenomena.

  C Price , T Hemmingsson , G Lewis , S Zammit and P. Allebeck
 

Background

Some studies suggest that cannabis use is associated with suicidal ideation, but no detailed longitudinal study has examined suicide as an outcome.

Aims

To examine the association between cannabis use and completed suicide.

Method

A longitudinal study investigated 50 087 men conscripted for Swedish military service, with cannabis use measured non-anonymously at conscription. Suicides during 33 years of follow-up were identified by linkage with the National Cause of Death Register.

Results

There were 600 (1.2% of cohort) suicides or deaths from undetermined causes. Cannabis use was associated with an increased risk of suicide (crude OR for ‘ever use’ 1.62, 95% CI 1.28–2.07), but this association was eliminated after adjustment for confounding (adjusted OR = 0.88, 95% CI 0.65–1.20).

Conclusions

Although there was a strong association between cannabis use and suicide, this was explained by markers of psychological and behavioural problems. These results suggest that cannabis use is unlikely to have a strong effect on risk of completed suicide, either directly or as a consequence of mental health problems secondary to its use.

  O Bennewith , T Amos , G Lewis , C Katsakou , T Wykes , R Morriss and S. Priebe
 

We assessed whether adult Black and minority ethnic (BME) patients detained for involuntary psychiatric treatment experienced more coercion than similar White patients. We found no evidence of this from patient interviews or from hospital records. The area (mental health trust) where people were treated was strongly associated with both the experience of coercion and the recording of a coercive measure in their records. Regarding charges of institutional racism in psychiatry, this study highlights the importance of investigating the role of area characteristics when assessing the relationship between ethnicity and patient management.

  S Hollinghurst , T. J Peters , S Kaur , N Wiles , G Lewis and D. Kessler
 

Background

Therapist-delivered online cognitive–behavioural therapy (CBT) has been found to be effective for depression in primary care.

Aims

To determine the cost-effectiveness of online CBT compared with usual care.

Method

Economic evaluation at 8 months alongside a randomised controlled trial. Cost to the National Health Service (NHS), personal costs, and the value of lost productivity, each compared with outcomes based on the Beck Depression Inventory and quality-adjusted life-years (QALYs). Incremental analysis indicated the NHS cost per QALY gain.

Results

Online CBT was more expensive than usual care, although the outcomes for the CBT group were better. Cost per QALY gain based on complete case data was £17 173, and £10 083 when missing data were imputed.

Conclusions

Online CBT delivered by a therapist in real time is likely to be cost-effective compared with usual care if society is willing to pay at least £20 000 per QALY; it could be a useful alternative to face-to-face CBT.

  D Rai , P Skapinakis , N Wiles , G Lewis and R. Araya
 

In a representative sample of the UK population we found that common mental disorders (as a group and in ICD–10 diagnostic categories) and subthreshold psychiatric symptoms at baseline were both independently associated with new-onset functional disability and significant days lost from work at 18-month follow-up. Subthreshold symptoms contributed to almost half the aggregate burden of functional disability and over 32 million days lost from work in the year preceding the study. Leaving these symptoms unaccounted for in surveys may lead to gross underestimation of disability related to psychiatric morbidity.

 
 
 
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