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Biomedical subjects

S Holt

Publications and source records attributed to S Holt.

At least 37 records · Page 2Linked to original sources

Trends in case-mix-adjusted use of radiology resources at an urban level 1 trauma center.

OBJECTIVE: The objective of our study was to determine the utilization rates of diagnostic radiology services at an urban level 1 trauma center. MATERIALS AND METHODS: This was an observational study of imaging use patterns from 1993 to 1998. Data were segregated by patient type and imaging procedure. Annual hospital admissions were adjusted for severity of illness using the Health Care Financing Administration's case-mix index. Per-patient imaging trends for the emergency department and outpatients were assessed using a ratio of the total number of procedures to the number of patient visits. Linear regression models were used to assess the strength of associations between resource use, measured as relative value units (RVUs), and independent variables (calendar year, patient type, and examination type). RESULTS: The RVUs for all imaging increased 53% for inpatients, 69% for outpatients, and 85% in the emergency department. No significant trend for use was found for the aggregate of inpatient imaging. There was a significant increase in the inpatient MR imaging RVUs (p = 0.04). No significant trend was found for the aggregated outpatient imaging RVUs. The trends were significant for angiography (p = 0.006), MR imaging (p = 0.002), and sonography (p = 0.04). The aggregated emergency room imaging RVUs showed a significant increase over time (p < 0.03). CONCLUSION: The number of imaging procedures increased during the study period. There was no overall trend toward increasing use of imaging in inpatients once an adjustment for severity of illness was made. Increases in patient visit-adjusted emergency department use of CT, sonography, and nuclear medicine procedures resulted from changes in practice patterns. For emergency department and outpatient settings, adjusting for the number of patient visits explains a significant portion of the increase in utilization.

Academic Medical Centers↗

The accuracy of references in Australian and New Zealand Medical Journals.

AIMS: Previous studies have found high error rates in references in biomedical journals. The aim of this paper was to assess the accuracy of references in three Australian and New Zealand general medical journals. METHODS: References from the August 1999 issues of the Medical Journal of Australia, the New Zealand Medical Journal and the Australian and New Zealand Journal of Medicine were assessed for accuracy using PubMed of the National Library of Medicine. RESULTS: This study found a high rate of reference errors in Australian and New Zealand medical journals. The reference error rate ranged from 33.5 to 48.8%. The most frequent errors were in the author's names and in the title. CONCLUSIONS: The reference error rate in Australia and New Zealand medical journals is high and is preventable. Authors should be more diligent and preferably verify cited references against the original article.

Australia↗

Deficiency of N-methylpurine-DNA-glycosylase expression in nonparenchymal cells, the target cell for vinyl chloride and vinyl fluoride.

The ability to repair promutagenic damage resulting from exposure to carcinogens is a critical factor in determining quantitative relationships in carcinogenesis, including the target cell for neoplasia. One major pathway for the repair of alkylating agent-induced DNA damage involves removal of alkylated bases by N-methylpurine-DNA-glycosylase (MPG), the first enzyme in base excision repair. We have measured the expression level of MPG mRNA in liver, lung, and kidney of Sprague-Dawley rats as a function of age. A quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) method was used to measure cellular MPG mRNA. MPG mRNA was readily detectable in each tissue analyzed and the age-dependent and tissue specific expressions were not statistically different. The lowest amount of mRNA was measured in preweanling liver and the highest amounts were found in preweanling lung and kidney. Since MPG is reported to be responsible for excision of 1,N(6)-ethenoadenine and N(2),3-ethenoguanine, two promutagenic DNA adducts of vinyl chloride (VC) and vinyl fluoride (VF), we examined the regulation of this enzyme after carcinogen exposure. Expression of MPG was induced in rat liver by these carcinogens. In order to determine the repair capacity in different cell populations of liver, we measured MPG gene expression in isolated hepatocytes and nonparenchymal cells (NPC). The amount of MPG mRNA was 4.5-5 times higher in hepatocytes than in NPC of control rats. Induction of MPG expression was observed in hepatocytes of VF exposed-rats but not in NPC. The expression of MPG in NPC was only 15% of that of the hepatocytes from exposed rats. Western blots of MPG protein confirmed the cell type differences, but did not show increased protein in exposed vs. control liver and hepatocytes. Since metabolism of VC and VF requires CYP2E1, an enzyme exhibiting much greater activity in hepatocytes, formation of etheno adducts preferentially occurs in hepatocytes. These data suggest that cellular differences in the repair of N-alkylpurines may be a critical mechanism in the development of cell specificity in VC carcinogenesis.

Aging↗

Asthma in New Zealand: myths and realities.

Asthma is a major health problem in New Zealand, generating large costs to the health services and industry. However, there are several myths concerning asthma in New Zealand. These are that it is more common and more severe in New Zealand than in the rest of the world, that it is more common in rural areas and that asthma mortality in New Zealand is the highest in the world. Using recently published data, it is now possible to show that none of these "facts" is true. In fact, asthma in New Zealand appears to have a prevalence and severity similar to those of the other major English-speaking countries and in this respect can be thought of as being first equal in the world. The relevance of correcting these myths is that they could influence future research. Previous research into the causes of asthma has sometimes focused on factors unique to New Zealand in an attempt to explain the increasing prevalence of asthma around the world. It may be more productive to direct future research towards identifying factors that the major English-speaking countries have in common.

Adolescent↗

Segmentation of 3D intravascular ultrasonic images based on a random field model.

Segmentation of intravascular ultrasound images provides important information about the degree of vessel obstruction as well as about the shape and size of plaques. To address the problems of inter- and intra-observer variances associated with conventional manual tracing, a fully automated segmentation was developed. The algorithm is based on the optimisation of a maximum a posteriori estimator, implementing the Rayleigh distribution of speckle and a priori information about the contours. Within 3D image sets, additional information by the blood flow resulting in a decorrelation of the pixels within the luminal boundary is used to initialise the segmentation. To accelerate the estimation, dynamic programming was used. The segmentation algorithm was realised as a Windows 95 application on a Pentium II/233 MHz and delivered reliable and reproducible results independent of the catheter position and the total image brightness (except overflow). In contrast, contours drawn by two physicians for an evaluation of 29 clinical cases showed large intra- and inter-observer variances. In vivo images were acquired with a 20 MHz transducer array (EndoSonics InVision). Comparison with the contours drawn by the physicians and histology demonstrates the potential of the segmentation algorithm.

Algorithms↗

Passive resistance of hamstring muscles in children with severe multiple disabilities?

The purposes of this study were to evaluate whether resistance to stretch could be measured in a reproducible manner from day to day in children with severe multiple disabilities, and whether 6 weeks of daily activity, including one daily stretch, would modify passive resistance to stretch. Passive resistance to stretch was measured in six children using an established model that synchronously and continuously measured knee flexion moment (Nm) and EMG activity of the hamstring, while the velocity and angle of a static stretch was controlled. Resistance to stretch was evaluated in the absence of EMG activity. Measurements were taken on two separate occasions with a 2-week hiatus, and before and after a 6-week activity period which included a daily 1-minute static stretch. There was no significant change in resistance to stretch when tested 2 weeks apart (test 1, 8.6 +/- 1.2 Nm; test 2, 8.3 +/- 1.2 Nm, p>0.05) which yielded a strong correlation coefficient (Spearman r=1.0, p<0.01; Pearson r=0.953, p<0.01). Similarly, there was no difference in resistance to stretch before and after the 6-week period (mean difference 0.22 +/- 0.75 Nm, p>0.05). Data from this study demonstrate that resistance to stretch of the hamstring muscle group could be measured in a reproducible manner from day to day in children with multiple disabilities. Further, resistance to stretch was unchanged after 6 weeks of daily activity, including a daily 1-minute static stretch.

Adolescent↗

A chemiluminescense-based assay for S-nitrosoalbumin and other plasma S-nitrosothiols.

The lack of a simple assay for the quantification of S-nitrosothiols in complex biological matrices has hampered our understanding of their contribution to normal physiology and pathophysiological states. In this paper we describe an assay based upon the release of nitric oxide by reaction with a mixture consisting of Cu(I), iodine and iodide with subsequent quantification by chemiluminescense. With this method we can detect levels of S-nitrosothiols down to 5 nM in plasma. Following alkylation of free thiols with N-ethylmaleimide, and removal of nitrite with acidified sulfanilamide, we were able to measure known amounts of S-nitrosoalbumin added to plasma or whole blood, with an inter-assay variation for plasma S-nitrosothiols of approximately 4%. Further studies showed that the mean concentration of circulating S-nitrosothiols in venous plasma of healthy human volunteers was 28+/-7 nM.

Adult↗

Influence of feeding regimen on body condition in the cat.

The influence of feeding regimen on body condition in the cat was studied in a sample of the UK domestic cat population (n = 136). Data were collected by interviewing cat owners and assessing body condition of cats in the owners' homes. Four main factors were identified which were related to body condition. These were, in descending order of significance: neuter status, age, frequency of treat feeding, and ad libitum feeding. Feeding regimen as a risk factor in feline obesity is discussed.

Animal Feed↗

Alcoholic hepatitis-the case for intensive management.

Alcoholic hepatitis is a common condition with a high mortality. Although treatment options for established alcoholic hepatitis are limited, many of the complications of this condition are preventable. This case report and discussion illustrate the important role of early diagnosis and intervention in this patient group. Important management points are stressed to aid physicians who may encounter this condition rarely.

Adult↗

Lipoic acid prevents development of the hyperdynamic circulation in anesthetized rats with biliary cirrhosis.

Chronic bile duct ligation is associated with the development of oxidant injury, biliary cirrhosis, portal hypertension, and a hyperdynamic circulation. We have previously demonstrated that the hyperdynamic circulation in the partial portal vein-ligated rat can be prevented by the administration of N-acetylcysteine. To extend these findings, we have examined the effect of lipoic acid, a thiol-containing antioxidant, on hemodynamics, oxidative stress, and nitric oxide (NO) production in bile duct-ligated (BDL) cirrhotic rats. Lipoic acid was given continuously in drinking water to normal and BDL rats; control rats received ordinary drinking water, and animals were studied at 24 days following surgery. Lipoic acid prevented the development of the hyperdynamic circulation (cardiac index [CI]: 15.7 +/- 2.0 vs. 29.5 +/- 2.1 mL x min-1 x 100 g-1; P <. 05) and significantly attenuated the rise in portal pressure (PP) (12.7 +/- 0.8 vs. 15.2 +/- 0.5 mm Hg; P <.05). Hepatic nitric oxide synthase (NOS) activity and plasma nitrite/nitrate concentration increased significantly following bile duct ligation, and both of these were prevented by lipoic acid. Lipoic acid had no effect on the biochemical or histological parameters of liver function in the cirrhotic group. We conclude that lipoic acid prevents the development of the hyperdynamic circulation in the rat model of biliary cirrhosis, and that this is associated with decreased synthesis of NO.

Animals↗

Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic Rat.

Sepsis is a common complication of cirrhosis with a high mortality. In this study, we have investigated some of the pathways that may be involved in tissue injury and death. Bile duct-ligated (BDL) cirrhotic and control rats were challenged with lipopolysaccharide (LPS). Sensitivity to LPS was markedly enhanced in the BDL group, and was associated with increased liver injury and mortality. There was a 5-fold constitutive activation of nuclear factor kappa B (NFkappaB) in the liver of BDL rat controls (P <.001), and this was activated further, but to a similar extent, in the liver of both sham and BDL rats after injection of LPS. Plasma tumor necrosis factor alpha (TNF-alpha) increased more markedly in the BDL cirrhotic rats (2,463 +/- 697 pg/mL in BDL rats versus 401 +/- 160 pg/mL in the controls at 3 hours; P <.01). Plasma nitrite/nitrate concentrations were increased in the BDL controls at baseline, and increased further after LPS (P <.05), but did not differ from sham controls at 6 hours. Plasma F(2)-isoprostanes increased 6-fold in the cirrhotic rats and 2-fold in the controls (P <.01) indicative of lipid peroxidation. Esterified F(2)-isoprostanes in the liver increased 2- to 3-fold at 1 hour in control and BDL rats, but returned to baseline levels by 3 hours. Esterified F(2)-isoprostanes in the kidney increased by 2-fold in the BDL rats after LPS administration, but remained unchanged in sham controls. We conclude that there is a marked increase in sensitivity to LPS in BDL cirrhotic rats. This is associated with an enhanced TNF-alpha response and increased lipid peroxidation. These may be directly and causally related to mortality.

Animals↗

Acute cholestasis-induced renal failure: effects of antioxidants and ligands for the thromboxane A2 receptor.

BACKGROUND: Acute biliary obstruction is associated with the development of renal impairment and oxidative stress. The F2-isoprostanes, formed during oxidant injury, are renal vasoconstrictors acting via thromboxane (TX)-like receptors. We determined whether the formation of F2-isoprostanes is increased in experimental cholestasis and whether thiol containing antioxidants or ligands for the TXA2 receptor could improve renal function. METHODS: The effects on renal function of acute bile duct ligation (BDL) in the rat were studied for two days. The consequences of administration of N-acetylcysteine (NAC), alpha-lipoic acid (LA), the TX receptor antagonist (TXRA) BAYu3405, or placebo were then examined. RESULTS: BDL caused a reduction in creatinine clearance from 1.10 +/- 0.05 to 0.55 +/- 0.05 ml/min and sodium excretion from 52 +/- 3 to 17 +/- 3 micromol/hr. Urinary F2-isoprostanes increased from 14 +/- 2 to 197 +/- 22 pg/ml following BDL. Renal functional changes were ameliorated by NAC (creatinine clearance 0.73 +/- 0.05 ml/min), LA (0.64 +/- 0.03 ml/min), and a TXRA (0.90 +/- 0.15 ml/min); P < 0.05. Similarly, sodium excretion was increased from 17 +/- 3 micromol/hr (placebo) to 34 +/- 3 micromol/hr (NAC), 29 +/- 3 micromol/hr (LA), and 38 +/- 5 micromol/hr (TXRA); P < 0.005. Hepatic glutathione concentrations increased from 6.5 +/- 0.3 micromol/g (normal liver) to 8.8 +/- 0.5 micromol/g (NAC) and 7.7 +/- 0.3 micromol/g (LA), P < 0.01. However, only LA markedly inhibited F2-isoprostane formation (197 +/- 22 to 36 +/- 11 pg/ml creatinine clearance; P < 0.05). Urinary TXB2 excretion was elevated after BDL (2.2 +/- 0.5 to 111.1 +/- 20.3 pg/min) but was unaffected by NAC and LA. CONCLUSION: NAC, LA, and TXRA can partially prevent renal dysfunction in experimental cholestasis. The effects of the antioxidants are independent of their ability to inhibit lipid peroxidation or TX synthesis.

Acetylcysteine↗