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Biomedical subjects

G Roche-Nagle

Publications and source records attributed to G Roche-Nagle.

12 recordsLinked to original sources

Pravastatin modulates early diabetic nephropathy in an experimental model of diabetic renal disease.

BACKGROUND: Development of diabetes causes early functional (endothelial dysfunction) and morphological abnormalities in the kidney. If left untreated, these will ultimately progress to renal failure. Apart from strategies aimed at maintaining very tight glycemic control, attention has turned to the development of adjuvant therapy to maintain endothelial function in these patients. The agents receiving the most critical appraisal due to their endothelial protective effects are the 3-hydrox 3-methylglutaryl (HMG)-Co-enzyme A (CoA) reductase inhibitors. The aim of the study was to investigate: (1) the early alterations in the renal diabetic injury; and (2) to examine the protective role of Pravastatin in this end-organ diabetic model. MATERIALS AND METHODS: Sprague Dawley rats (n = 21) were randomized into three groups: (1) control; (2) diabetic; and (3) diabetic treated with Pravastatin. Diabetic nephropathy was investigated with serum biochemical parameters (urea, creatinine), functional parameters (total urinary protein loss, glomerular filtration rate, renal cortical blood flow), and structural assessment (hemotoxylin and eosin staining). RESULTS: We demonstrated impairment in functional, biochemical, and structural parameters in the diabetic nephropathy group, which was diminished by treatment with Pravastatin. This was attributed to an up-regulation in endothelial constitutive nitric oxide synthase (ecNOS) expression in the treated diabetic group. CONCLUSIONS: We have shown that Pravastatin, in an experimental model of early diabetes nephropathy preserves microvascular endothelial function in the presence of hyperglycemia, thus inhibiting the early stage of diabetic microangiopathy.

Animals↗

Stump appendicitis: a rare but important entity.

A case of right lower quadrant pain in a 35-year-old male who underwent an appendicectomy 14 years previously is presented. Recurrent appendicitis with perforation was noted in an appendiceal stump on exploratory laparotomy. Although rare, inlammation of the appendiceal stump can occur and is still an important clinical entity. It is difficult to diagnose pre-operatively. A wide spectrum of causes in the differential diagnosis of right lower quadrant pain of the abdomen and a previous appendicectomy in a patient's history may delay the diagnosis. Knowledge of the condition should permit the physician to make an early diagnosis and, thus, limit the resultant morbidity.

Adult↗

Antimetastatic activity of a cyclooxygenase-2 inhibitor.

Cyclooxygenase-2 (COX-2) expression is increased in breast cancer and surgery has been shown to increase the growth of metastatic tumours. We investigated the effect of selective COX-2 inhibition on the growth of metastases in either an experimental metastasis model or following excision of a murine primary breast tumour. 50,000 4T1 mammary carcinoma cells were injected into the mammary fat pad of female BALB/c mice. When the mean TD reached 8+/-0.4 mm, tumours were excised and the mice were randomised into two groups (n=12 per group) to receive daily intraperitoneal injections of the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days. Alternatively, experimental metastases were established by tail-vein injection of 50,000 4T1 cells. Mice received either the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days (n=12 per group). SC-236 treatment significantly reduced tumour burden, the number and size of spontaneous metastases following primary tumour excision. SC-236 treatment also reduced tumour burden, the number and size of experimental metastases. Immunohistochemical staining demonstrated that COX-2 inhibition reduced microvessel density and increased apoptosis within both spontaneous and experimental metastases. These data clearly demonstrate that the selective COX-2 inhibitor, SC-236, has potent antimetastatic activity against both spontaneous metastases arising following primary tumour excision and experimental metastases.

Adenocarcinoma↗

Young male smokers have altered platelets and endothelium that precedes atherosclerosis.

BACKGROUND: Cigarette smoking results in abnormalities of platelets and endothelium with platelet dysfunction implicated in vascular complications. Healthy endothelium plays a pivotal role in regulating hemostasis via the inhibition of platelet activation and aggregation. Thus, we examined if platelet dysfunction correlated with serum vWF levels-a circulating marker of endothelial dysfunction. MATERIALS AND METHODS: We tested this hypothesis in young male smokers. The parameters of platelet function tested included: CD62/CD63; Glycoprotein (GP) IIb/IIIa; Platelet function analzyer (PFA) studies, platelet aggregometry, flow assessment of platelet microparticles, platelet-leukocyte interactions and receptor numbers. Endothelial dysfunction was assessed with serum von Willebrand Factor (vWF). RESULTS: There was a significant increase in platelet CD62 receptor expression and aggregation with an associated delay in time to aggregation using PFA. Endothelial dysfunction was represented by higher serum levels of von Willebrand Factor. All other platelet parameters tested were within the standardized reference range. CONCLUSIONS: These initial data suggests that anti-platelet therapy may have a role in reduction of platelet activation and aggregation in young smokers and possibly alter vascular endothelial abnormalities.

Adenosine Diphosphate↗

The European Working Time Directive: a survey of surgical specialist registrars.

On 1 August 2004 junior doctors in the Irish health care system and other healthcare systems throughout Europe will no longer be excluded from the provisions of the European Working Time Directive. Their working hours will then be limited by law, first to 58 hours a week and then, by 2009, to 48 hours. This will demand even more profound changes for the Irish health care system than seen so far. This survey was undertaken to elicit the opinions and first-hand experiences of surgical specialist registrars (SpRs) throughout Ireland on different working patterns, and the impact of being on-call on their surgical training and lives. The working time directive will undoubtedly shake the foundations of surgery in Ireland and Europe, and meeting the directive by 2009 will require fundamental change if both it and the challenge of providing first class surgical training and safe patient care are to be met.

Attitude of Health Personnel↗

Unusual cause of a perforated stomach.

A case of gastric perforation 2 months following insertion of a gastric balloon is reported. The literature is reviewed regarding the complications and success rates inherent in such balloon devices. This is the first case report of an intra-gastric balloon causing gastric perforation.

Female↗

Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancer.

The effect of selective and non-selective cyclo-oxygenase inhibition on tumour growth and metastasis in an orthotopic model of breast cancer was investigated. 4T1 mammary adenocarcinoma cells were injected into the mammary fat pad of female BALB/c mice. When tumours reached a mean tumour diameter of 8.4+/-0.4 mm, mice were randomised into three groups (n=6 per group) and received daily intraperitoneal injections of the selective cyclo-oxygenase-2 inhibitor, SC-236, the non selective cyclo-oxygenase inhibitor, Indomethacin, or drug vehicle. Tumour diameter was recorded on alternate days. From 8 days after initiation of treatment, tumour diameter in animals treated with either SC-236 or indomethacin was significantly reduced relative to controls. Both primary tumour weight and the number of lung metastases were significantly reduced in the SC-236 and indomethacin treated mice. Microvessel density was reduced and tumor cell apoptosis increased in the primary tumour of mice treated with either the selective or non-selective cyclo-oxygenase inhibitor. In vitro, cyclo-oxygenase inhibition decreased vascular endothelial growth factor production and increased apoptosis of tumour cells. Our results suggest that cyclo-oxygenase inhibitors will be of value in the treatment of both primary and metastatic breast cancer.

Adenocarcinoma↗

Nail-gun limb injuries.

We present four cases and a review of the literature regarding nail-gun related limb injury. Nail guns have significant potential to cause limb and other major injuries. In most cases improper use of the nail-gun is the single most important factor in causing such types of injuries. Treatment of these injuries requires careful assessment of the limb and the type of nail involved in order to enable safe extraction. We recommend the introduction of training in the workforce to encourage awareness of the danger of such devices. We also emphasize the continuing requirements for improved workplace safety and adequate safety equipment when working with such dangerous devices.

Accidents, Occupational↗

Virtual reality technology and surgical training--a survey of general surgeons in Ireland.

BACKGROUND: Virtual Reality Technology (VRT) is a validated method of training in industry but only recently has found a place in the postgraduate surgical curriculum. AIMS: We surveyed 143 Irish consultant surgeons to ascertain their opinions on this topical issue. METHODS: The survey consisted of 22 questions to which the consultants were asked to respond by choosing from a 5-point Likert scale. RESULTS: Sixty-five per cent responded. A majority of 72% had seen VRT but only 47% had 'hands on' experience. Forty-six per cent believed that they were poorly informed regarding available technologies. As consultants became more informed about VRT significant differences were seen with regard to attitudes regarding the role of VR in skills in surgical training (p<0.05) and in the ability to define teaching objectives (p<0.005). CONCLUSIONS: Our survey suggests that the underuse of the current offerings is not due to a perceived lack of interest on the part of the surgical trainers. Suppliers of these programmes have a responsibility to adequately educate and collaborate with all parties involved to improve overall benefit from these simulators.

Clinical Competence↗

Nicorandil related anal ulcer.

BACKGROUND: Anal ulceration is uncommon. Patients are typically referred because of severe anal pain, bleeding, discharge, and ulceration. It is important to exclude anal carcinoma, and to consider more unusual causes. METHODS: A 74-year-old lady presented with severe anal pain and ulceration. This was subsequently noted to be related to nicorandil, a potassium channel activator used in the treatment of angina. Discontinuation of nicorandil and faecal diversion allowed symptom relief and ulcer healing. CONCLUSION: Knowledge of the association between nicorandil and anal ulceration is essential in order to appropriately diagnose and manage this condition.

Aged↗

Evaluation of patient knowledge regarding oral anticoagulants.

Warfarin sodium [Coumadin] is widely used since its introduction in 1954. The dosage varies from individual to individual and is subject to adjustment due to interactions with other medications and alcohol. It is therefore important for the patient to be educated fully regarding warfarin therapy as outside the narrow therapeutic range either failure to prevent thromboembolism or serious bleeding with potential fatal complications may occur. Patient comprehension of the risks of anticoagulation, tablet recognition skills and knowledge of complications of warfarin therapy were evaluated in 150 patients attending the anticoagulation clinic in a Dublin teaching hospital. The majority, 125 (83%) perceived that they had received education about the therapy. Concomitant aspirin was avoided by 125 (83%) patients, but 25 (17%), thought it safe in combination with warfarin; 33 (22%) believed that alcohol was safe in combination with warfarin. When asked about the colours and strengths of warfarin tablets, 125 (83%) patients identified the 1 mg tablet correctly. Only 105 (70%) identified the 3 mg tablet and 98 (65%) the 5 mg tablet correctly. In 42 (28%), patients could not describe their current therapy. Potential complications from over- and under-dosage with warfarin were unknown to 89 (59%) and 90 (60%) patients respectively. This study suggests that patient knowledge regarding anticoagulation therapy is not optimal. A significant group may be at risk from serious complications because of inadequate knowledge. We suggest improving patient knowledge may improve control, reduce complication and therefore reduce the burden on the health service.

Anticoagulants↗