Appendicolith revealed on CT in children with suspected appendicitis: how specific is it in the diagnosis of appendicitis?

OBJECTIVE. The purpose of this study was to determine the sensitivity, specificity, and positive and negative predictive values of a diagnosis of appendicitis when CT without enteric contrast material reveals an appendicolith in children with suspected appendicitis. MATERIALS AND METHODS. A retrospective review of children who underwent abdominal CT for suspected appendicitis over a 25-month period was performed to identify patients with an appendicolith. An age-matched group of patients examined for trauma served as controls. RESULTS. CT was performed in 104 children. Appendicitis was present in 60 (58%) of 104 children; 39 (65%) of 60 had an appendicolith. Appendicitis was not present in 44 (42%) of 104; six (14%) of 44 had an appendicolith. An appendicolith detected on CT had a sensitivity of 65% and a specificity of 86% for the radiologist diagnosing appendicitis. An appendicolith had a positive predictive value of 74% and a negative predictive value of 26%. Among the control population, two (3%) of 74 children had an appendicolith. This number was statistically significant compared with children in the study group with an appendicolith and abdominal pain, but without appendicitis (p = 0.02). CONCLUSION. Although an appendicolith is significantly associated with appendicitis, the detection of an isolated appendicolith on CT is not sufficiently specific to be the sole basis for the diagnosis of acute appendicitis.     

Nowhere To Go But Up: The Return of Medicinal Chemistry

Medicinal chemistry, as a field, has moved into new andunwelcometerritory. How did we get here, and what might be the way out?     

Failure to Detect a DNA Repair-related Defect in the Transfection of Ataxia-telangiectasia Cells by Enzymatically Restricted Plasmid

Summary

We have transfected two SV40-transformed human fibroblast cell lines with plasmids in which double-strand breaks have been introduced by restriction enzymes, within or near the selected gene. Restriction of pSV2gpt with KpnI, as previously shown by Cox et al. (1986), reduced the frequency of transfection more in the ionizing radiation-sensitive ataxia-telangiectasia line AT5BIVA than in the resistant line MRC5V1. When the related plasmid pSV2neo was restricted with SmaI, the reduction in transfection was less in the ataxia-telangiectasia than in the normal cell line. Under our conditions, the apparent defect in transfection of AT5BIVA by pSV2gpt appears to be a result of the unusual sensitivity of the repair-deficient recipient to the selective agent. Loss of potential transfectants is exacerbated when transient gene expression is reduced by restriction of the plasmid. We suggest that a reduction in yield of transfectants with restricted plasmid in ataxia-telangiectasia cells cannot readily be used as evidence of a defect in DNA repair. Our results are also relevant to standard transfection experiments, since they emphasize the importance of optimizing selection when transient expression may be reduced, to ensure that potential transfectants are not killed by the selection regime.     

Inclusion body myositis: an underdiagnosed condition?

Inclusion body myositis is an increasingly recognised form of inflammatory myopathy with characteristic clinical and histopathological features which has seldom been reported in the United Kingdom. This paper presents the clinicopathological features of a series of patients diagnosed in Nottingham from 1986 to 1990. During this period, 1319 muscle biopsy samples were processed by this laboratory and rimmed vacuoles were seen in 17 patients. Eleven patients had definite or probable inclusion body myositis according to published criteria. The mean age of the group was 69.4 years with a male to female ratio of 8:3. Typical clinical features were a slowly progressive painless, proximal lower limb weakness, with muscle wasting and early loss of reflexes. The median duration of illness from first symptom to presentation was five years (range 2-18 years). Falls were a prominent symptom in six patients and distal weakness occurred in nine patients. Creatine kinase was increased in 10 patients but only one had a level > 1000 IU/l; the erythrocyte sedimentation rate was normal in five patients. Treatment with steroids or cytotoxic drugs, or both, did not prevent disease progression. It is confirmed that inclusion body myositis is a distinct cause of inflammatory myopathy which is probably underdiagnosed in the United Kingdom. Clinically, it should be suspected in older patients presenting with muscle weakness of insidious onset. Pathologically, a careful search should be made for rimmed vacuoles and inflammation; ultrastructurally, the presence of inclusions will confirm the diagnosis.     

Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease: Edinburgh Artery Study.

AIMS: Recently, markers of inflammation, haemostasis, and blood rheology have received much attention as risk factors for coronary heart disease and stroke. However, their role in peripheral arterial disease (PAD) is not well established and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6), have not been examined before in prospective epidemiological studies. METHODS AND RESULTS: In the Edinburgh Artery Study, we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were recruited. After 17 years, 208 subjects had developed symptomatic PAD. In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and haematocrit [hazard ratio (95% CI) corresponding to an increase equal to the inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22 (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index. Other markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue plasminogen activator antigen, and plasma and blood viscosities showed weak associations, which were considerably attenuated when CVD risk factors were accounted for. CONCLUSIONS: Our prospective data showed that several inflammatory, haemostatic, and rheological markers are associated with incident PAD; however, their clinical utility is likely to be limited. Future research is necessary to validate the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations.     

Femoral atherosclerosis in an older British population: prevalence and risk factors

Most estimates of the prevalence of peripheral atherosclerosis have been based on intermittent claudication or lower limb blood flow. The aim of this study was therefore to determine the prevalence of underlying femoral plaque, and to determine its association with other cardiovascular disease and risk factors. Presence of plaque was identified using ultrasound in a random sample of men (n=417) and women (n=367) aged 56-77 years. Coexistent cardiovascular disease, exercise and smoking were determined by questionnaire, blood pressure was recorded, and serum cholesterol and plasma fibrinogen were determined. Of the 784 subjects that were scanned, 502 (64%) demonstrated atherosclerotic plaque. Disease prevalence increased significantly with age (P<0.0001), and was more common in men (67.1 vs. 59.4%, P<0.05). Subjects with femoral plaque had a significantly greater odds of previous ischaemic heart disease (OR 2. 2, 95% CI 1.3, 3.7) and angina (OR 1.7, 95% CI 1.03, 2.7), but not of stroke or leg pain on exercise. Current and ex-smoking, raised serum total cholesterol and plasma fibrinogen levels, but not blood pressure, were associated with an increased risk of femoral plaque, independent of age and sex. Frequent exercise and a high HDL cholesterol were significantly associated with lower risk. In conclusion, therefore, atherosclerotic disease of the femoral artery affects almost two-thirds of the population in late middle age. It is associated with an increased prevalence of ischaemic heart disease and angina, but whether detecting at risk individuals using ultrasound offers advantages over simpler and less expensive risk factor scoring requires evaluation in trials.     

Tobacco smoke exposure, wheeze, and atopy

We investigated the effect of in utero and postnatal environmental tobacco smoke (ETS) exposure on respiratory symptoms and atopy in the first 3 years of life in children at high risk of allergic disease (both parents atopic). Three hundred and sixty-nine children were followed from birth and reviewed at ages 1 and 3 years (respiratory questionnaire, skin testing). Parental smoking questionnaires were administered, and plasma cotinine in cord and peripheral blood (at age 1 year) was measured (capillary column gas-liquid chromatography). Wheezing starting in the first year of life was significantly more common in children of smoking mothers (54.2% vs. 39.5%, P = 0.017), but not wheezing starting after age 1 year (10.8% vs. 10.9%, smoking and nonsmoking mothers, P = 0.99). Detectable cord cotinine was not associated with wheeze. More frequent wheeze in infancy was significantly more common in those with detectable 1-year cotinine (e.g., wheeze without colds, 17.8% vs. 5.6%, P = 0.02; wheeze most days, 6.5% vs. 0%, P = 0.04). ETS exposure was not associated with atopy. In the multivariate regression analysis, maternal smoking during pregnancy and/or in the first year of life remained associated with wheeze in the first year of life (odds ratio, 1.88; 95% confidence interval, 1.14-3.12; P = 0.01). ETS exposure in "high-risk" infants increases the risk of wheezing starting in the first year of life, but not after age 1 year. However, ETS exposure has little or no effect on the development of atopy. Measurement of plasma cotinine was no more useful than tobacco exposure assessment by questionnaire in our cohort.     

Mapping of quantitative trait loci for hypnotic sensitivity to ethanol in crosses derived from the C57BL/6 and DBA/2 mouse strains

BACKGROUND: Acute ethanol sensitivity is thought to be a predisposing factor toward the development of alcoholism. Accumulated evidence suggests that this characteristic may be at least partly heritable. A widely accepted approach for identifying genes thought to contribute to alcoholism is to map quantitative trait loci (QTLs) for various ethanol-related behaviors in rodent models. METHODS: Ethanol sensitivity QTLs were interval-mapped in a C57BL/6 (B6) X DBA/2 (D2) F2 intercross that contained 391 mice. Sensitivity was measured as the duration of loss of righting reflex (LORR) after 4.1 g/kg ip. LORR also was evaluated in a chromosome 1 marker-assisted congenic strain that had an approximately 30 centiMorgan (cM) portion of D2 DNA from the distal end of chromosome 1 introgressed onto a B6 background. RESULTS: A suggestive QTL was mapped on chromosome 1 (LOD = 3.3; approximately 80 cM) and a provisional QTL on chromosome 5 (LOD = 2.3; approximately 26 cM). The provisional chromosome 5 QTL was found to be sex-specific (LOD = 2.5 for males; LOD < 1 for females) with the D2 allele increasing LORR. The chromosome 1 D2 allele decreased LORR. Consistent with the F2 QTL mapping, congenic mice heterozygous for the chromosome 1 interval (B6/D2) had a significantly different mean (+/- SEM) LORR of 74.0 +/- 4.9 min (n = 36) compared with 90.8 +/- 6.2 min (n = 33) for their homozygous (B6/B6) littermates (p = 0.02). Blood ethanol concentration at regain of righting reflex was 377 +/- 10 mg% for the B6/D2 and 368 +/- 10 mg% (p = NS) for the B6/B6. CONCLUSIONS: LORR results in the chromosome 1 congenic mice were consistent with and very similar to what was predicted from the QTL analysis in the B6 X D2 F2 population. These results support a suggestive LORR QTL on the distal end of mouse chromosome 1. The results also indicate that there is a provisional sex-specific LORR QTL on chromosome 5.