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Biomedical subjects

S C Weight

Publications and source records attributed to S C Weight.

16 recordsLinked to original sources
PubMed2002

Optimizing surveillance mammography following breast conservation surgery.

AIMS: Prompt detection and treatment of local recurrence (LR) following breast conservation surgery (BCT) may improve subsequent survival. Following early reports demonstrating increased LR in the first years after surgery, a practice of surveillance mammography starting 1 year from diagnosis has become established. Increasing use of adjuvant chemotherapy with adriamycin-containing regimens has resulted in radiotherapy being postponed, so that the first mammogram coincides with the acute radiotherapy reaction, resulting in patient discomfort and poor quality films. We wished to determine if the 1-year mammogram could safely be omitted. METHODS: We reviewed 1151 consecutive patients treated with BCT for in situ, stage I or II disease over a 10-year period. All patients had clear resection margins and, where indicated, underwent axillary surgery and adjuvant treatment. This consisted of radiotherapy (40 Gy with a 5 Gy boost), chemotherapy and/or tamoxifen. RESULTS: Overall, the 5-year actuarial rate of local recurrence was 4.8%. The cumulative risk of LR at 12 months was 0.3% (three patients) and 1.9% (20 patients) at 24 months. This included all cases of high-grade DCIS (>30 mm in size) and all but one tumour with a Nottingham Prognostic index (NPI) of >6.0 which recurred locally. CONCLUSION: Even including those patients generally accepted to be at high risk of LR, the cumulative risk of LR was only 0.3% at 12 months from surgery. We now therefore schedule routine biennial mammography from time of surgery except for those with high risk of early local recurrence such as extensive, high-grade in situ disease.

Breast Neoplasms↗
PubMed2001

Interaction of eicosanoids and nitric oxide in renal reperfusion injury.

BACKGROUND: Both the eicosanoids and nitric oxide are known to play an important role in the pathogenesis of postischemic injury. Recent evidence has suggested that the generation of each may affect the other via a feedback loop. This was investigated in an experimental model of renal warm ischemia reperfusion injury. METHODS: Rats underwent bilateral renal warm ischemia (15-60 min) then reperfusion (20 or 80 min) followed by a unilateral nephrectomy to measure renal nitric oxide (as nitroxides) and eicosanoids. Renal function was measured on days 2 and 7 prior to terminal nephrectomy for tissue analysis. RESULTS: Vasodilator eicosanoids (6-KPGF1alpha and PGE2) fell on reperfusion in line with the duration of warm ischemia with a concomitant rise in the vasoconstrictor TxA2. The ratio of vasodilator to vasoconstrictor eicosanoids fell from 8.22 (2.3) in the control to 0.82 (0.1) in the 60-min warm ischemia group (P<0.01). Renal levels of nitroxides rose on reperfusion demonstrating an inverse correlation with the eicosanoid ratio (r2=0.86). Renal function was impaired at both day 2 and day 7 and showed a positive correlation with the eicosanoid ratio (r2=0.67 and 0.62, respectively). CONCLUSIONS: Renal warm ischemic injury is associated with a progressive fall in the ratio of vasodilator-to-vasoconstrictor eicosanoids from early in reperfusion through to day seven although nitric oxide was elevated throughout the same period. There was no evidence of coinduction of nitric oxide synthase and cyclooxygenase in this model.

Animals↗
PubMed2000

Pulmonary nitric oxide metabolism following infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury.

OBJECTIVES: to investigate endogenous pulmonary nitric oxide metabolism following infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury. METHODS: groups of male Wistar rats (n=6) were subjected to 60 minutes of infrarenal aortic cross-clamping under general anaesthesia. Rats were culled after 0, 60 and 120 minutes>> reperfusion, following release of the aortic clamp. A sham-operated control group was also studied. Acute lung injury (ALI) was quantified by measuring the protein concentration in lung bronchoalveolar lavage (BAL) fluid. Pulmonary myeloperoxidase activity (MPO) was measured as an index of neutrophil infiltration and degranulation in the lung. Plasma tumour-necrosis factor-alpha (TNF-alpha) was measured as an index of the pro-inflammatory cytokine response and pulmonary nitric oxide synthase (NOS) activity was determined by measuring conversion of(3)H L-arginine to(3)H L-citrulline in tissue homogenates. RESULTS: these data show significant ALI with increased pulmonary microvascular permeability and MPO activity in animals subject to 60 minutes>> ischaemia and 60 minutes or 120 minutes of reperfusion compared to control animals (p<0.01). Plasma TNF-alpha levels were significantly increased following 60 minutes of ischaemia compared to controls (p<0.01) and remained significantly increased in animals subject to reperfusion (p<0.01). Pulmonary NOS activity was significantly increased in animals subject to reperfusion (p<0.01). CONCLUSIONS: the reperfusion phase of infrarenal aortic cross-clamping provokes a significant increase in pulmonary NOS metabolism. The increase in plasma TNF-alpha and MPO activity suggests that this response may be secondary to inducible NOS expression. Manipulation of this response may benefit patients at risk of acute injury following infrarenal aortic reconstruction.

Animals↗
PubMed2000

Prevention of renal impairment following aortic cross-clamping by manipulation of the endogenous renal nitric oxide response.

OBJECTIVE: Infrarenal aortic cross-clamp-induced lower torso ischaemia-reperfusion injury is associated with impairment of glomerular filtration rate and upregulation of endogenous renal nitric oxide production. The aim of this study was to investigate whether manipulation of the endogenous renal nitric oxide response can ameliorate subsequent renal injury. METHODS: Groups of male Wistar rats (n = 6) were treated with one of the following agents before being subjected to 60 min of infrarenal aortic cross-clamping: saline (control), L-NMMA (a pan nitric oxide synthase inhibitor), 1400W (a highly selective iNOS inhibitor), hydrocortisone (an inhibitor of the systemic inflammatory response), L-arginine (the substrate for nitric oxide synthase) and NOC-18 (a nitric oxide donor). Animals were recovered after a left nephrectomy. The glomerular filtration rate (GFR) of the remaining kidney was measured on the second and seventh postoperative day using a 99Tc DPTA clearance technique as an index of renal injury. RESULTS: Animals treated with L-NMMA prior to aortic cross-clamping had a significantly impaired GFR compared to controls on the second (p<0. 01, Mann-Whitney U -test) and seventh (p<0.05, Mann-Whitney U -test) postoperative day. Hydrocortisone and 1400W had no significant effect on GFR on the second or seventh postoperative day. L-arginine and NOC-18 had no influence on GFR on the second postoperative day but significantly improved GFR on the seventh postoperative day. CONCLUSIONS: These results show that the endogenous nitric oxide response protects the kidneys from ischaemia-reperfusion injury. Manipulation of the renal nitric oxide response may have therapeutic benefits to patients undergoing aortic aneurysm repair by preventing acute renal failure.

Animals↗
PubMed2000

A modification to aid open tracheostomy.

Open tracheostomy is performed less frequently thereby increasing the likelihood of morbidity, e.g. bleeding. The simple modification described aids the technical process and minimises problems with the procedure.

Humans↗
PubMed1999

Endogenous renal nitric oxide metabolism following experimental infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury.

BACKGROUND: Abdominal aortic surgery is associated with marked changes in renal haemodynamics. The aim of this study was to investigate the influence of infrarenal cross-clamping on glomerular filtration rate and endogenous renal nitric oxide metabolism. METHODS: Groups of male Wistar rats were subjected to infrarenal aortic cross-clamping followed by reperfusion. Animals were allowed to recover after a left nephrectomy. The glomerular filtration rate of the remaining kidney was measured on the second and seventh day after the procedure before the animal was killed and the remaining kidney harvested. Total nitric oxide synthase (NOS) activity and expression of inducible NOS (iNOS) was determined in renal tissue following 1 h and 7 days of reperfusion. RESULTS: Glomerular filtration rate was impaired on the second and seventh day after operation in all animals subjected to lower torso ischaemia compared with controls (P < 0.05). Renal NOS activity was increased at 1 h and 7 days in animals subjected to infrarenal cross-clamping compared to controls (P < 0.01). iNOS was detected in renal tissue of animals subjected to infrarenal aortic cross-clamping on the seventh day after operation. CONCLUSION: Infrarenal aortic cross-clamping is associated with impairment of renal function in the early postoperative period. There is an increase in endogenous renal nitric oxide metabolism with iNOS expression. Presented in part to the Surgical Research Society, Dublin, Ireland, July 1998

Animals↗
PubMed1999

Biphasic role for nitric oxide in experimental renal warm ischaemia-reperfusion injury.

BACKGROUND: Whilst nitric oxide has a clearly defined role in renal haemostasis, debate continues over its pathophysiology. This study investigated the function of nitric oxide in a model of renal warm ischaemia-reperfusion injury. METHODS: Rats underwent bilateral renal warm ischaemia (45 min) after pretreatment with nitric oxide donors, nitric oxide synthase (NOS) inhibitors or saline (control). Following reperfusion (20 min) a unilateral nephrectomy was performed to measure renal nitric oxide (as nitroxides) and oxidative DNA and protein damage. Renal function was measured on days 2 and 7 before terminal nephrectomy for analysis and morphology. RESULTS: The increase in renal nitric oxide level seen early in reperfusion (20 min) (P < 0.01) was prevented by inhibition of constitutive (cNOS) but not inducible (iNOS) NOS. The increase in oxidative damage (P < 0.01) was exacerbated by nitric oxide donors (P < 0.01) but ameliorated by NOS inhibition (P < 0.01). Control nitric oxide remained increased through to day 7 (P < 0.01) but was reduced by nitric oxide donors and cNOS inhibitors (P < 0.05). Oxidative damage returned towards normal in the control group, whereas both DNA and protein damage persisted following NOS inhibition (P < 0.01). CONCLUSION: Inhibition of the postischaemic increase in the level of nitric oxide was associated with an early decrease in, but eventual exacerbation of, oxidative damage. This suggests the prolonged increase in renal nitric oxide concentration was cytoprotective overall.

Animals↗
PubMed1998

Nitric oxide and renal reperfusion injury: a review.

BACKGROUND: Nitric oxide (NO) is a ubiquitous molecule with a role in both normal homeostasis and pathophysiological processes. However, the role it plays in renal ischaemia reperfusion injury is matter of some contention. METHOD AND RESULTS: This paper précis the biology and biosynthesis of NO before concentrating on the function of NO in renal ischaemia reperfusion injury. What emerges is a picture of some clarity about the normal physiological role of NO but some discord regarding the generation and function of postischaemic nitric oxide. Some of the reasons for this are explored in more detail. CONCLUSIONS: Clarity on the precise effect of postischaemic NO will remain elusive without the in vivo measurement of NO in experimental models.

Animals↗
PubMed1998

New model of renal warm ischaemia-reperfusion injury for comparative functional, morphological and pathophysiological studies.

BACKGROUND: Renal warm ischaemia-reperfusion injury is pertinent to vascular and transplant surgery. While established models provide functional and morphological data the authors wanted to be able to correlate this with the underlying pathophysiology at any chosen time point, thus allowing future interventional effects on reperfusion injury to be evaluated. METHODS: In a rodent model bilateral renal warm ischaemia (15-60 min) and then reperfusion (20 or 80 min) before nephrectomy allowed for analysis of early reperfusion pathophysiology. The remaining kidney provided functional data (glomerular filtration rate (GFR)) at days 2 and 7 before nephrectomy for late analysis and morphology using a new grading system. RESULTS: Acceptable survival rate (ten of 12 animals) was seen with up to 45 min of warm ischaemia. Renal function was impaired at day 2 following 30-60 min of warm ischaemia (P< 0.01) and day 7 in the 45- and 60-min groups (P < 0.05 and P < 0.01 respectively). Strong correlation existed between duration of ischaemia and GFR at day 2 (r2=0.88) and day 7 (r2=0.95). Histological damage in the cortical tubules was evident in the 45- and 60-min groups (P< 0.01). CONCLUSION: This new model allowed comparative functional, morphological and pathophysiological studies while minimizing the number of animals required. Overall 45 min of warm ischaemia gave significant, recoverable injury and is recommended for investigating renal reperfusion injury.

Animals↗
PubMed1998

Nitric oxide generation is increased in experimental renal warm ischaemia-reperfusion injury.

BACKGROUND: Nitric oxide has a clearly defined place in normal renal homoeostasis while there is a continuing debate as to its role under pathophysiological conditions. This study investigated the role of nitric oxide in a model of renal warm ischaemia-reperfusion injury. METHODS: Groups of rats underwent bilateral renal warm ischaemia (for 15-60 min) followed by reperfusion (20 or 80 min) before unilateral nephrectomy for measurement of renal nitric oxide (as nitroxides) and oxidative damage. Renal function was measured on days 2 and 7 before killing and nephrectomy. A further group received the nitric oxide synthase inhibitor N(G)-nitro L-arginine methyl ester (L-NAME; 50 mg per kg body-weight) before induction of warm ischaemia. RESULTS: In early reperfusion there was a correlation between the duration of warm ischaemia (15-45 min) and renal nitrate (r2=0.97) which increased from a mean(s.e.m.) baseline value of 95(5.9) to 208(17.3) nmol per mg protein following 45 min of warm ischaemia. Levels were further raised at 80 min and maintained through to day 7 (241(12.5) nmol per mg protein in 45-min group). This rise was attenuated by L-NAME (P< 0.01) as was the early rise in oxidative damage seen otherwise. By day 7, however, oxidative damage was increased (all P< or = 0.01). CONCLUSION: Renal nitric oxide increased early in recoverable warm ischaemia-reperfusion injury and remained raised to day 7. Nitric oxide synthase inhibition ameliorated early but exacerbated late damage suggesting that the early burst of nitric oxide is cytotoxic but that overall nitric oxide may exert a cytoprotective effect.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Digital ischaemia: an unusual presentation of dysbarism.

Dysbaric symptoms following ascent from a scuba dive are due to symptomatic nitrogen or air emboli with clear patterns of associated injury. This case report highlights an unusual presentation of dysbaric injury treated successfully with a prostacyclin analogue.

Adolescent↗
PubMed1997

Colonic Strongyloides stercoralis infection masquerading as ulcerative colitis.

Strongyloides stercoralis is a nematode infection which predominantly involves the small bowel. Spillover infection to the colon does occur, but is uncommon and is usually associated with an immunocompromised host. Accurate diagnosis is essential and, as this case demonstrates, a long history does not preclude an infective aetiology.

Animals↗
PubMed1996

Renal ischaemia--reperfusion injury.

Ischaemia-reperfusion injury is a complex interrelated sequence of events that classically involves the vascular endothelium and activated leucocytes. During the ischaemic phase the endothelium is primed both to produce free radicals and to secrete chemoattractants. The resultant neutrophil sequestration serves to amplify the injury, but damage is not confined to the postischaemic area and more generalized effects typically follow. The situation in the kidney is complex for, while ischaemia primes the tissue for reperfusion damage, it also causes early and irreversible tubular injury. Furthermore, it appears that relatively less importance should be attached to the involvement of neutrophils than at other sites, and relatively more to a local postischaemic imbalance in the levels of nitric oxide and endothelin. Despite a greater understanding of the pathogenesis of ischaemia-reperfusion injury, effective treatment remains elusive and research is hampered by apparent species and organ-specific differences.

Free Radicals↗