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Biomedical subjects

K Hamilton

Publications and source records attributed to K Hamilton.

At least 19 recordsLinked to original sources

Use of a temporary cohort ward as part of an intervention to reduce the incidence of meticillin-resistant Staphylococcus aureus in a vascular surgery ward.

This article describes the effect of introducing a cohort area into a vascular surgery ward where a sustained increase in new cases of meticillin-resistant Staphylococcus aureus (MRSA) made the implementation of standard MRSA infection control precautions untenable. A recent review of published reports concluded, 'that little evidence could be found to suggest that isolation measures recommended in the UK are effective'. The authors recommended a reporting format to enable the evidence for isolation to be gathered more systematically. This paper follows the recommended reporting format. The setting was a 30-bedded acute and subacute vascular surgery ward within a tertiary care hospital in Glasgow, UK. The data were analysed as an interrupted time series of 19 months pre-cohort, eight months with cohort and eight months post cohort. Following the instigation of the cohort area, there was a significant reduction in the number of nosocomial MRSA isolates from patients (P=0.0005). This reduction was sustained after the cohort area was discontinued. In conclusion, effective separation of MRSA-colonized/-infected patients from patients who are not colonized/infected with MRSA, using a cohort area, resulted in a significant reduction in MRSA cross-colonization and cross-infection. The resulting reduction in MRSA prevalence within the unit facilitated effective screening and isolation of subsequent patients once the cohort area had been discontinued.

Cross Infection↗

CFD simulation of a novel bileaflet mechanical heart valve prosthesis: an estimation of the Venturi passage formed by the leaflets.

The aim of this study was to validate the flow characteristics of the novel Helmholtz-Institute Aachen Bileaflet (HIA-BL) heart valve prosthesis. The curved leaflets of the HIA-BL valve form a Venturi passage between the leaflets at peak systole. By narrowing the cross section the flow accelerates and the static pressure at the central passage decreases according to the Venturi effect. The low-pressure zone between the leaflets is expected to stabilize the leaflets in fully open position at peak systole. To investigate the Venturi passage, the flow fields of two valve geometries were investigated by CFD (Computational Fluid Dynamics): one geometry exhibits curved leaflets resulting in a Venturi passage; the other geometry features straight leaflets. The flow profiles, pressure distribution and resulting torque of both passages were compared and investigated. Although flow profiles downstream of both valves were similar, the flow passages between the leaflets were different for the investigated leaflet geometries. The straight leaflet passage showed a large boundary layer separation zone near the leaflets and the lowest pressure at the leading edge of the leaflet. The Venturi passage showed a reduction of the boundary layer separation zones and the lowest pressure between the leaflets could be found in the narrowest flow cross section of the Venturi passage. Additionally, the resulting torque showed that the Venturi passage produced an opening momentum. The results demonstrate that the Venturi passage stabilizes the leaflets in open position at peak systole.

Blood Flow Velocity↗

An 8 year study of risk factors for SIDS: bed-sharing versus non-bed-sharing.

BACKGROUND: It is unclear if it is safe for babies to bed share with adults. In Ireland 49% of sudden infant death syndrome (SIDS) cases occur when the infant is bed-sharing with an adult. OBJECTIVE: To evaluate the effect of bed-sharing during the last sleep period on risk factors for SIDS in Irish infants. DESIGN: An 8 year (1994-2001) population based case control study of 287 SIDS cases and 831 controls matched for date, place of birth, and sleep period. Odds ratios and 95% confidence intervals were calculated by conditional logistic regression. RESULTS: The risk associated with bed-sharing was three times greater for infants with low birth weight for gestation (UOR 16.28 v 4.90) and increased fourfold if the combined tog value of clothing and bedding was > or =10 (UOR 9.68 v 2.34). The unadjusted odds ratio for bed-sharing was 13.87 (95% CI 9.58 to 20.09) for infants whose mothers smoked and 2.09 (95% CI 0.98 to 4.39) for non-smokers. Age of death for bed-sharing and sofa-sharing infants (12.8 and 8.3 weeks, respectively) was less than for infants not sharing a sleep surface (21.0 weeks, p<0.001) and fewer bed-sharing cases were found prone (5% v 32%; p = 0.001). CONCLUSION: Risk factors for SIDS vary according to the infant's sleeping environment. The increased risk associated with maternal smoking, high tog value of clothing and bedding, and low z scores of weight for gestation at birth is augmented further by bed-sharing. These factors should be taken into account when considering sleeping arrangements for young infants.

Adult↗

Diabetes in rat pregnancy alters renal calcium and magnesium reabsorption and bone formation in adult offspring.

AIMS/HYPOTHESIS: We tested the hypothesis that diabetes in pregnancy can result in the in-utero reprogramming of renal calcium and magnesium handling and of bone formation in the offspring, which persists into adulthood. METHODS: Male offspring of streptozotocin-treated diabetic rats (OD rats) and of control non-diabetic animals (OC rats) were investigated as neonates and at 8, 12 and 16 weeks of age. RESULTS: Compared with OC rats, urinary calcium and magnesium output was significantly reduced in OD rats at every age studied; Na+ and K+ outputs were unaffected. The renal expression of proteins involved in the tubular reabsorption of calcium (calcium ATPase, calbindin-D28k and epithelial calcium channel) was increased in OD animals compared with that in OC animals. Additionally, we observed that adult OD rats had lower trabecular and higher cortical femoral bone volumes, explained by deposition of bone on the endosteal surface. CONCLUSIONS/INTERPRETATION: These data show that diabetes in pregnancy has profound effects on male offspring in terms of renal tubular calcium and magnesium reabsorption and the normal pattern of bone formation. These effects persist into adulthood. Such long-lasting effects of diabetes on kidney and the skeleton were not suspected and could have important implications for the health of children born to diabetic women.

Aging↗

Altered expression of iron transport proteins in streptozotocin-induced diabetic rat kidney.

Diabetes mellitus is associated with altered iron homeostasis in both human and animal diabetic models. Iron is a metal oxidant capable of generating reactive oxygen species (ROS) and has been postulated to contribute to diabetic nephropathy. Two proteins involved in iron metabolism that are expressed in the kidney are the divalent metal transporter, DMT1 (Slc11a2), and the Transferrin Receptor (TfR). Thus, we investigated whether renal DMT1 or TfR expression is altered in diabetes, as this could potentially affect ROS generation and contribute to diabetic nephropathy. Rats were rendered diabetic with streptozotocin (STZ-diabetes) and renal DMT1 and TfR expression studied using semi-quantitative immunoblotting and immunofluorescence. In STZ-diabetic Sprague-Dawley rats, renal DMT1 expression was significantly reduced and TfR expression increased after 2 weeks. DMT1 downregulation was observed in both proximal tubules and collecting ducts. Renal DMT1 expression was also decreased in Wistar rats following 12 weeks of STZ-diabetes, an effect that was fully corrected by insulin-replacement but not by cotreatment with the aldose reductase inhibitor, sorbinil. Increased renal TfR expression was also observed in STZ-diabetic Wistar rats together with elevated cellular iron accumulation. Together these data demonstrate renal DMT1 downregulation and TfR upregulation in STZ-diabetes. Whilst the consequence of altered DMT1 expression on renal iron handling and oxidant damage remains to be determined, the attenuation of the putative lysosomal iron exit pathway in proximal tubules could potentially explain lysosomal iron accumulation reported in human diabetes and STZ-diabetic animals.

Animals↗

Early and late mortality after myocardial infarction in men and women: prospective observational study.

OBJECTIVE: To compare characteristics, management, and outcome of myocardial infarction (MI) in men and women. DESIGN: Prospective observational study. SETTING: District general hospital in southwest Scotland. PARTICIPANTS: 966 men and 597 women admitted with first MI between 1994 and 2000 with follow up to the end of 2001. RESULTS: 393 (40.7%) men and 305 (51.1%) women died during a median follow up of 3.4 years for the survivors. Univariate analysis indicated an excess mortality among women (hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.25 to 1.68), which disappeared after adjustment for age, smoking, co-morbidity, previous vascular disease, diabetes, hypertension, and social deprivation (HR 1.02, 95% CI 0.87 to 1.20). There was also an excess early mortality within 30 days among women (HR 1.54, 95% CI 1.20 to 1.98), though this did not retain significance after adjustment for the same covariates (HR 1.04, 95% CI 0.79 to 1.37). Small and insignificant differences were found in the proportion of men and women receiving thrombolysis on admission and secondary prophylactic drugs at discharge, except for statins and beta blockers, which were respectively more (adjusted odds ratio 1.48, 95% CI 1.10 to 1.98) and less (adjusted odds ratio 0.78, 95% CI 0.60 to 1.00) commonly prescribed to women. CONCLUSION: Results suggest that the poorer outcome for women after MI reported in other studies may reflect sex bias in management as well as differences in age and co-morbidity and support the view that if women have access to the same quality of care as men then survival will be the same.

Age Factors↗

An audit of nutritional care delivered to elderly inpatients in community hospitals.

BACKGROUND: There is continuing concern over the lack of attention to the nutritional needs of older people in hospitals. A 2-year audit project was undertaken to examine the nutritional care of inpatients in Leicestershire Community Hospitals. METHOD: The methods used included analysis of menu cycles; observation of meal and drink provision, wastage, supplement usage and portion sizes; and patient satisfaction questionnaire examination. RESULTS: Patient menus were nutritionally inadequate for energy, fibre and vitamin D, and protein levels were variable. The percentage of meal wastage and inadequate portion sizes were of concern. Patient satisfaction results were overall positive. CONCLUSION: Patient energy intakes are a major concern with low calorie provision from menus exacerbated by a deficit in recommended portion sizes and a high percentage of meal wastage. Routine audits need to be implemented to monitor both portion size and meal wastage, and to address patient satisfaction issues to improve the overall intakes of patients. Multidisciplinary team input is required to address the above issues and additional recommendations to promote nutrition as a key component in clinical care.

Aged↗

gamma-Linoleic acid and ascorbic acid ameliorate the effects of experimental diabetes on electrolyte and bone homeostasis in pregnant rats.

Experimental diabetes in rats is associated with excessive electrolyte loss in the urine, which is further accentuated by pregnancy, particularly of Ca. Supplementation with essential fatty acids and antioxidants has proven beneficial in treating several types of complications, including nephropathy. The present study investigated the effect of gamma-linoleic acid (GLA; 500 mg/kg per day; group DG) and ascorbate (290 mg/kg per day; group DA), alone and in combination (group DGA), as well as ascorbyl-GLA (790 mg/kg per day; group DASG), on urinary electrolyte output and skeletal composition in pregnant streptozotocin-diabetic rats. Urine was collected in metabolism cages before and throughout pregnancy. Diabetic rats (DP) increased their urine volume as compared with control (CP) throughout the experiment, reaching an output of more than 13 times that of the control group by the end of pregnancy (CP 24+/-4, DP 316+/-21, DG 223+/-21, DA 221+/-14, DASG 163+/-17, DGA 220+/-19 ml urine/24 h). Concomitant with increased urine volume was a reduction of urinary Na (CP 47+/-14, DP 22+/-5 mmol/l), K (CP 210+/-34, DP 31+/-1 mmol/l) and Mg (CP 14+/-1, DP 3.8+/-0.2 mmol/l) concentration, but not of Ca concentration (CP 5.4+/-1.5, DP 6.3+/-0.6 mmol/l), and hence total Ca loss was relatively most severe. All the treatments reduced urine volume with no effects on electrolyte concentration as compared with DP, with no significant difference between the treatments. A reduced bone size and bone Ca content was partially ameliorated by the diet supplementation. We have concluded that GLA and ascorbate, alone or in combination, prevent urinary electrolyte loss in pregnant rats and do so by reducing urine production.

Animals↗

High-performance liquid chromatography/mass spectrometry characterization of Ki4B-Ras in PSN-1 cells treated with the prenyltransferase inhibitor L-778,123.

Cellular transformation by Ras oncoproteins requires the posttranslation modification of farnesylation in a reaction catalyzed by farnesyl protein transferase (FPTase). Thus, inhibitors of FPTase have been developed as potential anticancer agents. However, recent studies with selective inhibitors of FPTase have shown that Ki4B-Ras retains its ability to transform cells by undergoing alternative prenylation by the related geranylgeranyl protein transferase I (GGPTase-I) in human tumor cells. We have developed a high-performance liquid chromatography/mass spectrometry assay for the detection and quantitation of the different processing states of Ki4B-Ras isolated from PSN-1 cells (a human pancreatic cell line with an activating Gly12 to Arg mutation) treated with the prenyltransferase inhibitor, L-778,123. Recently tested in the clinic, L-778,123 is a potent inhibitor of FPTase (in vitro IC50 = 2 nM) with some activity against GGPTase-I (in vitro IC50 = 98 nM). We find primarily farnesylated-Ki4B-Ras in vehicle-treated PSN-1 cells, a mixture of farnesylated- and geranylgeranylated-Ki4B-Ras in cells treated with nanomolar concentrations of L-778,123, and a mixture of unprocessed, farnesylated, and geranylgeranylated-Ki4B-Ras in cells treated with micromolar concentrations of compound. Of importance, this technique does not require metabolic labeling and may be used as a pharmacodynamic assay for Ki4B-Ras processing in mouse models.

Alkyl and Aryl Transferases↗

Short-term exercise improves myocardial tolerance to in vivo ischemia-reperfusion in the rat.

These experiments examined the independent effects of short-term exercise and heat stress on myocardial responses during in vivo ischemia-reperfusion (I/R). Female Sprague-Dawley rats (4 mo old) were randomly assigned to one of four experimental groups: 1) control, 2) 3 consecutive days of treadmill exercise [60 min/day at 60-70% maximal O2 uptake (VO2 max)], 3) 5 consecutive days of treadmill exercise (60 min/day at 60-70% VO2 max), and 4) whole body heat stress (15 min at 42 degrees C). Twenty-four hours after heat stress or exercise, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was maintained for 30-min followed by a 30-min period of reperfusion. Compared with control, both heat-stressed animals and exercised animals (3 and 5 days) maintained higher (P < 0.05) left ventricular developed pressure (LVDP), maximum rate of left ventricular pressure development (+dP/dt), and maximum rate of left ventricular pressure decline (-dP/dt) at all measurement periods during both ischemia and reperfusion. No differences existed between heat-stressed and exercise groups in LVDP, +dP/dt, and -dP/dt at any time during ischemia or reperfusion. Both heat stress and exercise resulted in an increase (P < 0.05) in the relative levels of left ventricular heat shock protein 72 (HSP72). Furthermore, exercise (3 and 5 days) increased (P < 0.05) myocardial glutathione levels and manganese superoxide dismutase activity. These data indicate that 3-5 consecutive days of exercise improves myocardial contractile performance during in vivo I/R and that this exercise-induced myocardial protection is associated with an increase in both myocardial HSP72 and cardiac antioxidant defenses.

Animals↗

Myocardial infarction in men and women under 65 years of age: no evidence of gender bias.

We examined short and long term outcomes of MI in a consecutive series of 169 men and 50 women who were followed for an average of 3.5 years. Similar percentages of men and women were admitted to medical intensive care, received in-patient cardiac rehabilitation, quit smoking at one year, were still smoking, were taking a lipid lowering drug or had returned to work at one year, underwent coronary angiography at 3.5 years or had died by 3.5 years. The lack of gender difference in outcome may reflect an absence of gender bias in the management of men and women with MI in southwest Scotland.

Age Factors↗

Empathy deficits and cognitive distortions in child molesters.

An attempt was made to examine the thesis that the apparent empathy deficits in child molesters are simply another aspect of their self-serving tendency to distort information by, in this case, failing to recognize victim harm. Thirty-four child molesters were compared on a victim empathy measure and a measure of cognitive distortions, with 24 nonsex offenders and 28 nonoffending males. Child molesters displayed greater cognitive distortions than the other subjects and their greatest empathy deficits were toward their own victims. Consistent with the theory being examined it was found that the empathy scores of the child molesters toward their own victims were significantly correlated with the responses to the cognitive distortions scale. The results are discussed in terms of their implications for theory and practice.

Adult↗

Effect of pregnancy on exposure to malaria mosquitoes.

Pregnant women attracted twice the number of Anopheles gambiae complex--the predominant African malaria-carrying mosquito--than did their non-pregnant counterparts. We postulate that physiological and behavioural changes that occur during pregnancy are responsible for increased attractiveness, which could be important in intervention strategies aimed at protecting this high-risk group against malaria.

Analysis of Variance↗

Prevalence and prognostic significance of neuroendocrine cells in esophageal adenocarcinoma.

Neuroendocrine differentiation is common in adenocarcinomas of the stomach and colon and may be associated with a slightly better prognosis in gastric adenocarcinoma. We studied neuroendocrine differentiation in esophageal adenocarcinomas and associated Barrett's esophagus (BE) to determine association with patient outcome. Fifty-eight cases of esophageal adenocarcinoma (15 biopsies, 43 resections) from 52 patients were stained with a monoclonal antibody to chromogranin (CG). Medical records were reviewed for tumor stage, response to therapy, and patient survival. Thirty-two patients received radiation and chemotherapy, and four received radiation. Twelve of 58 (20.7%) esophageal adenocarcinomas contained scattered CG-positive cells. Tumors with CG-positive cells were moderately to poorly differentiated, and many consisted of large cribriform glands, similar to intestinal-type adenocarcinomas. One case of small cell carcinoma of the esophagus was weakly CG positive; another was negative. Neuroendocrine differentiation was retained in lymph node metastases in two cases but lost in three other cases. In 10 CG-negative primary tumors, lymph node metastases were also negative. For five of six patients with paired biopsy/resection specimens, no CG-positive cells were seen in either specimen; one patient had CG-positive cells only in the resection. There was no difference in tumor stage at surgery or survival time between CG-positive and CG-negative tumors. BE was present in 34 cases and contained CG-positive cells in 21 of 34 (61.8%). Low-grade dysplasia contained CG-positive cells in 11 of 14 cases (78.6%) and high-grade dysplasia in 3 of 6 cases. Fourteen of 21 (66.7%) adenocarcinomas associated with CG-positive BE were negative for CG. In summary, neuroendocrine differentiation is common in BE and is retained in low- and high-grade dysplasia but is usually lost in esophageal adenocarcinoma. The presence of scattered neuroendocrine cells does not affect patient outcome.

Adenocarcinoma↗

Primary intracerebral Hodgkin's disease mimicking meningioma: case report.

OBJECTIVE AND IMPORTANCE: A rare case of dura-based primary cerebral Hodgkin's disease clinically and radiographically indistinguishable from a meningioma is described. CLINICAL PRESENTATION: A 55-year-old immunocompetent woman presented with headaches and ataxia. Magnetic resonance images demonstrated a circumscribed diffusely enhancing mass with a dural tail attached to the cerebellar tentorium. INTERVENTION: Operative inspection also suggested a meningioma, but a frozen section of the firm mass revealed an inflammatory lesion. Subsequent pathological analysis demonstrated Hodgkin's disease, nodular sclerosing type. An extensive workup revealed no systemic disease. CONCLUSION: This case illustrates the rare occurrence of primary intracranial Hodgkin's disease and its mimicry of meningioma.

Brain Neoplasms↗

Tumour necrosis factor-alpha blockade: a new era for effective management of rheumatoid arthritis.

Tumour necrosis factor (TNF)-alpha inhibitors have emerged as a new treatment option for rheumatoid arthritis (RA). The scientific rationale for targeting TNF-alpha in RA derives from extensive work in the laboratory, showing the importance of this pro-inflammatory cytokine as a mediator of joint inflammation. Proof of principle has now been firmly established in clinical trials where TNF-alpha inhibitors have been shown to decrease the signs and symptoms of joint inflammation and slow radiological progression of joint damage. Presently, the two TNF-alpha inhibitors available for use in RA are etanercept and infliximab. Etanercept is a soluble TNF receptor: Fc fusion protein that competes with the endogenous TNF receptors for TNF-alpha binding. Infliximab is a chimeric anti-TNF-alpha monoclonal antibody, which also binds with high affinity to soluble TNF-alpha. Etanercept and infliximab will be rapidly incorporated into current treatment paradigms, which call for early and intensive treatment of RA using disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, sulfasalazine and hydroxychloroquine. A major drawback to the widespread use of these biologics is their high costs. Some patients with limited financial means may be denied access to these effective anti-inflammatory agents. Moreover, long-term experience with TNF-alpha inhibitor therapy has been limited and concerns linger about the possibility that etanercept and infliximab may cause unforeseen side effects or increase the risk for opportunistic infection. Despite these caveats, TNF-alpha inhibitors represent a major advance for the treatment of RA and will likely spawn new indications for anti-TNF-alpha therapy and the development of novel therapeutic compounds with similar biological activity.

Antibodies, Monoclonal↗

Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy.

Offspring of rats with diabetes mellitus are at risk of reduced calcium and bone mineral content. Altered expression of the maternal calcium binding proteins, calbindin-D(9K) and calbindin-D(28K), which are involved in renal and placental calcium transport, may underlie these problems.We have investigated the effect of diabetes on circulating concentrations of regulatory hormones with respect to calbindin-D mRNA concentrations. Three rat groups were studied; control (CP), streptozotocin-induced diabetic (DP), and insulin-treated diabetic (DPI) pregnant rats. Calbindin-D(9K) and calbindin-D(28K) mRNA abundance in placenta and maternal kidney were measured at days 7, 15, 18 and 21 of gestation, together with serum or plasma concentrations of 1,25 dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)), parathyroid hormone (PTH), PTH-related protein (PTHrP), calcitonin, oestradiol and IGF-I. An increase in placental calbindin-D(9K) mRNA abundance between days 18 and 21 in CP and DPI rats was severely blunted in the DP rats. In contrast, renal calbindin-D(28K) mRNA abundance was greater at days 7, 15 and 18 in DP compared with CP rats, as was calbindin-D(9K) at day 18. Calcitonin concentrations showed no differences between the groups, and both PTH and IGF-I were reduced over the first half of gestation, unlike the calbindins. In contrast, the concentrations of PTHrP and 1,25(OH)(2)D(3) were reduced at term in the DP group compared with the other two groups. Plasma oestradiol concentrations were lower in DP than in CP rats at days 7, 15 and 18, and most striking was the absence in DP rats of the peak of oestradiol seen at day 18 in CP rats. Despite the similarity between changes in placental calbindin mRNA and 1,25(OH)(2)D(3), previous work has shown placental calbindin-D(9K) regulation to be vitamin-D-independent. These studies produce suggestive evidence, therefore, that PTHrP and oestradiol may be involved in the altered calbindin-D expression by kidney and placenta in rat diabetic pregnancy.

Animals↗