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Biomedical subjects

F Scott

Publications and source records attributed to F Scott.

At least 19 recordsLinked to original sources

Recent molecular advances in the approach to early lung cancer detection and intervention.

Lung cancer is a major contributor to overall cancer mortality. Detecting lung cancer while it is still a localized process is a long-cherished goal for improving the outcome of this disease. Recent developments suggest that we are approaching this capability. We next have to think about how to implement a change in our approach to lung cancer management to derive the benefit of better detection capability. This is an area in which our growing understanding of lung cancer biology is providing clues on improving the inhibition of cancer progression.

Apoptosis

Resolution of hydrops in twin-twin transfusion syndrome: could steroids have a role?

A case of twin-twin transfusion is presented with hydrops occurring twice in the recipient twin and resolving. Polyhydramnios was treated with numerous volume-reducing amniocenteses (amnioreductions), which were performed prior to both occurrences of hydrops. Amnioreductions were only performed before the first resolution of hydrops, whereas betamethasone was given prior to both episodes of hydrops resolving. Steroids may be useful not just in case of premature delivery but also to help a compromised fetus cope in utero.

Adult

Adverse reactions to food constituents: allergy, intolerance, and autoimmunity.

Food allergies and intolerance represent important health concerns to consumers who are predisposed to these illnesses. Unlike many current food safety issues, food sensitivities are complicated by both complex and multiple individual adverse reactions, which can vary from emotional to pathophysiological ailments. In some instances, the underlying mechanisms that result in the development of food allergies or intolerance have marked differences but produce common symptoms. The present-day diagnosis of these disorders can be impeded by intrinsic limitations in generating accurate information from patient history and biochemical, physicochemical, and immunochemical tests. Oral challenge tests represent effective methods for confirming and testing food allergens and food intolerance; however, these procedures are often restricted to clinical trials. It is important to be able to distinguish among food allergy, intolerance, and autoimmune disease in the management of these disorders. The role of food in the development of autoimmune disease may be exemplified by celiac disease, a food-induced enteropathy, requiring exposure to prolamins in wheat, rye, and barley. Various wheat and soy protein sources, including the soy protein isolates used to make infant formulas, have been related to juvenile or insulin-dependent diabetes mellitus (IDDM), a common chronic disease of childhood. Employing food process technologies to eliminate food constituents with potential for intolerance in some individuals is a potentially viable approach for reducing risk to food-related disorders. Finally, the development of food labelling regulations that require the identification of potential food allergens or agents for intolerance in the ingredient declaration on prepackaged food is a positive step toward the prevention of severe adverse reactions in hypersensitive individuals.

Animals

Detection of K-ras oncogene mutations by polymerase chain reaction-based ligase chain reaction.

To evaluate a rapid multiplexed assay to detect three common K-ras codon 12 mutations, primer pairs complementary to the wild-type and mutant loci were developed and tested with lung cancer cell lines with previously identified mutation status. The sensitivity of detection of mutations was determined to be at least 1% using spiked samples containing K-ras codon 12 mutations. This assay was then used to evaluate prospectively K-ras status in airways of individuals at high risk of lung cancer by analysis of bronchoalveolar lavage (BAL) specimens from patients who have been previously treated for lung cancer. DNA was extracted from BAL specimen cell pellets, and PCR-based ligase chain reaction was performed for mutations in the first position of codon 12 of K-ras, with positive and negative controls. Of 10 BAL samples, 4 contained 1 mutation (GGT --> TGT), 1 contained 2 mutations (GGT --> TGT and GGT --> AGT), and the rest were wild-type. The BAL mutations were validated by cloning and screening with mutant-specific probes followed by confirmation sequencing.

Bronchoalveolar Lavage

Establishment and application of a normal range for nuchal translucency across the first trimester.

Before chorionic villus sampling at 10-13 weeks' gestation, 453 women had the crown-rump length and nuchal translucency (NT) measured with transabdominal ultrasound. There were 19 aneuploid pregnancies (ten cases of trisomy 21, six of trisomy 18, one of 47 + marker, one 47,XXX, and one 45,X mosaic). Average NT was 1.7 mm (range 0-5 mm), correlating with the crown-rump length, but not maternal age. A static cut-off of 2.5 mm gave a false-positive rate of 1.3 per cent for crown-rump length between 30 and 35 mm, rising to 13 per cent in fetuses with a crown-rump length between 50 and 65 mm. This gave an overall false-positive rate of 5.5 per cent for a detection rate of 30 per cent for trisomy 21. Applying a dynamic action limit (95th centile), the false-positive rate remained at 5 per cent irrespective of the crown-rump length, detecting 30 per cent of trisomy 21 and 36.8 per cent of all aneuploidies. Raising the action limit to the 97.5th centile halved the false-positive rate (2.5 per cent), with no change in trisomy 21 detection and only a slight decrease in aneuploidy detection (31.6 per cent). Aneuploid fetuses showed normal first-trimester growth. NT increases with gestational age, making a dynamic action limit necessary to decrease the false-positive rate, while maintaining aneuploidy detection rates. Aneuploidy does not cause significant first-trimester growth retardation, enabling normal ranges for NT with crown-rump length to apply.

Adult

A decade of experience with Mycobacterium tuberculosis culture from children: a seasonal influence on incidence of childhood tuberculosis.

SETTING: A tertiary care hospital in the Western Cape Province of South Africa from November 1983-October 1993. OBJECTIVE: Evaluation of the source of all cultures of Mycobacterium tuberculosis from children aged < 13 years and documentation of the mean time for culture with Löwenstein-Jensen (LJ) medium and a radiometric method (Bactec). RESULTS: One thousand six hundred and sixty cultures of M. tuberculosis were obtained from 1204 children (638 (53%) males and 566 (47%) females). The median time to a positive culture result was 65 days with LJ medium and 23 days with Bactec (P < 0.0001). Gastric aspirate provided 1298 cultures (78%) from 983 children (82%) of whom 52% were aged < 2 years. Ninety-six positive sputum specimens were from 79 children (7%) of whom 70% were > 5 years. Significantly more positive cultures were obtained during the late winter and early spring (P < 0.001), and a similar trend was found for tuberculous meningitis. CONCLUSION: The use of a radiometric culture method has expedited the confirmation of tuberculosis in childhood in our hospital. Even in children < 3 months of age the diagnosis of tuberculosis can often be confirmed by culture. The documented increase in childhood tuberculous disease in spring suggests an increased transmission of tuberculous infection in autumn and winter in our community.

Age Distribution

An investigation into the application and maintenance of Hamilton Russell traction on three orthopaedic wards.

This study is concerned with the application and maintenance of Hamilton Russell traction, a form of vectored skin traction. It may be used in the treatment of fractures of the femur for the purposes of immobilization and for pain relief prior to surgery. A preliminary questionnaire demonstrated a poor level of knowledge in nurses working in an orthopaedic area. It was therefore speculated that application and maintenance of the traction would be inaccurate. The angles making up the resultant traction forces were measured in 11 systems. The theoretical traction force was established using mathematics. The actual force was measured using a goniometer. A comparison was then made. The results in all 11 systems demonstrated a highly statistically significant difference between the theoretical and actual positions of the traction force (P < 0.0005). The practical implications of this are discussed and recommendations for a protocol of application and maintenance suggested. Areas for further research are identified.

Biomechanical Phenomena

First trimester aneuploidy screening using nuchal translucency, free beta human chorionic gonadotrophin and maternal age.

Screening for aneuploidy using maternal age has a low detection rate and high false positive rate. Second trimester maternal serum screening increases trisomy 21 detection and decreases the false positive rate. First trimester screening would enable definitive diagnosis with chorionic villus sampling, and simple surgical termination of affected pregnancies would still be an option. Nuchal translucency (NT), free beta human chorionic gonadotrophin (f beta HCG) and maternal age were assessed in 302 patients before chorionic villus sampling. NT positively and f beta HCG negatively correlated with gestation, but neither correlated with maternal age nor with each other. Both NT and f beta HCG were increased in trisomy 21. NT was increased and f beta HCG was decreased in trisomy 18. Multivariate discriminant analysis enabled 87.5% detection of trisomy 21 in this high-risk population, for a 14% false positive rate. In a simulated normal population, using a risk cut-off of 1 in 250, 71% detection was achieved for a 7% false positive rate. The combination of NT, f beta HCG and maternal age is a simple, readily available and viable first trimester screening strategy.

Adult

Accuracy of estimated fetal weight below 1,000 g.

The Warsof formula is 1 of 3 currently recommended by the Australian Society for Ultrasound in Medicine for the routine estimation of fetal weight. However, this formula was derived using mostly large fetuses, and its accuracy in extremely low birth-weight fetuses is not known. Using this formula, we studied 184 infants delivering within 14 days of an estimated fetal weight (EFW) < 1,000 g. The mean percent error in EFW was 11.7% underestimation, with 80% of infants underestimated and 61% of estimates within 15% error. The percent error was consistent at 9.6% throughout the first 9 days, but increased to 32% after 10 days post scan (p < 0.0001). There was a significant association between the accuracy of EFW and maternal height, but not with placental position, liquor volume or multiple pregnancy. EFW underestimated birth-weight on average by 9.6% during the first week, and this error appeared to be mainly due to the formula. The error in EFW became unacceptable after 9 days and repeating the estimate before 10 days is recommended. A different formula may be more suitable for extremely low birth-weight fetuses.

Birth Weight

New formula for estimating fetal weight below 1000 g: comparison with existing formulas.

Most estimated fetal weight formulas have been derived and tested with larger fetuses, yet accuracy in predicting birth weight is more critical at the limit of viability. Complete data from 142 pregnancies in which delivery took place within 7 days of an ultrasonographic examination were used to create an appropriate formula for fetuses less than 1000 g and compare it with 10 currently available formulas. Our formula (In [BW] = 0.66 x 1n [HC] + 1.04 x 1n [AC] + 0.985 x 1n [FL]) was significantly more accurate than all other formulas and also performed better on a prospective cohort of 27 fetuses with estimated fetal weight less than 1000 g. Of the existing formulas, the Hadlock formula (using head circumference, abdominal circumference, femur length) was the most accurate, being significantly more accurate than all but the Woo formula with all but the Woo formula.

Birth Weight

Thiamine status in patients receiving long-term home parenteral nutrition.

OBJECTIVES: Clinical thiamine deficiency can occur in patients receiving total parenteral nutrition (TPN) without thiamine supplementation. Because considerable breakdown of thiamine may occur in the presence of bisulfite-containing amino acid solutions, subclinical thiamine deficiency may develop with the use of these solutions, even with appropriate thiamine supplementation. The current American Medical Association-Food and Drug Administration approved injectable multivitamin formula contains 3 mg of thiamine. This study was undertaken to determine whether this quantity of thiamine is sufficient to avoid clinical thiamine deficiency in long-term home TPN patients with negligible oral thiamine absorption and in the presence of bisulfite-containing amino acid solutions. METHODS: Twenty-four long-term home TPN patients with oral caloric intakes below the norm were evaluated. Seventeen patients suffered from short bowel syndrome or radiation enteritis, and another three had draining gastrostomies that precluded all intestinal absorption. The duration of TPN therapy ranged between 1 and 164 months. Thiamine status was assessed by assaying thiamine pyrophosphate, transketolase activity, and blood thiamine levels. RESULTS: All thiamine pyrophosphate and erythrocyte transketolase activity levels were within the normal range. CONCLUSIONS: This study demonstrates that the currently recommended 3 mg of thiamine hydrochloride added to TPN solutions is adequate to maintain normal thiamine status. This should prevent the development of thiamine deficiency even in patients with compromised intestinal thiamine absorption, and in the presence of bisulfite-containing amino acid solutions.

Adult

Distal gangrene in a polycythemic recipient fetus in twin-twin transfusion.

BACKGROUND: Gangrene of an extremity in a twin pregnancy has been attributed to the release of thromboplastin from a dead fetus or to a combination of polycythemia and anomalous vasculature. It has not been described in a situation where both twins survived. CASE: In a pregnancy complicated by twin-twin transfusion syndrome and managed with repeated amniocenteses, both twins survived. The recipient twin had necrosis of the left lower leg, which had appeared in the antenatal period and was associated with polycythemia, but not anomalous vasculature. CONCLUSION: Antenatally, polycythemia alone may cause necrosis of an extremity. Necrosis could be detected with ultrasound examination and may be an additional argument for laser photocoagulation of the chorioangiopagus.

Adult

Maternal serum screening and routine 18-week ultrasound in the detection of all chromosomal abnormalities.

Over a 15-month period, maternal serum screening (alpha fetoprotein, oestriol, chorionic gonadotrophin) and ultrasound were evaluated in the detection of all chromosomal abnormalities. Of the 981 screened, there were 8 chromosomally abnormal pregnancies. Six of these were considered to be at increased risk on serum screening, all of which were detected. Of the remaining 2, one was detected by ultrasound and the other resulted in a liveborn baby with trisomy 21. The positive and negative predictive values for serum screening for all chromosomal abnormalities was 7.8% and 99.9% respectively. The sensitivity and specificity was 87.5% and 91.5% respectively. Serum screening is useful in the detection of many chromosomal abnormalities, not just Down syndrome. The combination of maternal serum screening and ultrasound has a high negative predictive value and is valuable in providing reassurance of no underlying chromosomal abnormality. With a positive predictive value of 7.8% a chromosomal abnormality will be found once in every 13 amniocenteses performed.

Adult

Molecular markers in early cancer detection. New screening tools.

Better early detection strategies for lung cancer are clearly needed. About 20 years ago, cytomorphologic criteria were developed for use in staging bronchial epithelium carcinoma. Yet, when sputum cytology was added to chest radiograph in the largest early-screening-of-lung-cancer study carried out to date, the three-arm trial sponsored by the National Cancer Institute, no major outcome benefit was shown. Sputum samples of participants in one of these trials, the Johns Hopkins Lung Project, have been archived. Currently, sputum immunostaining using two monoclonal antibodies directed at a difucosylated Lewis X epitope and a 31-kilodalton protein show correlation between positive staining of these samples and eventual development of lung cancer in the sampled population. Strategies to neutralize the stimulation of growth factors like gastrin-releasing peptide, which are seen in small-cell disease, are also being explored. Development of an epithelial-directed diagnostic test is the most important goal in obtaining early detection tools for lung cancer. Several new tests await prospective trials to evaluate their utility. In developing an early detection test for lung cancer, due to the chronic nature of the risk and the vast at-risk population, cost and patient compliance are two major concerns.

Antibodies, Monoclonal

Chronic hepatitis C virus infection in haemophilic patients: clinical significance of viral genotype.

We have undertaken a comprehensive study of hepatitis C virus (HCV) genotype and its clinical significance in haemophilic patients. 189 HCV RNA positive were typed, using the Simmonds classification scheme, by restriction fragment length polymorphism (RFLP) in an amplified segment of the 5' non-coding region of the HCV genome. Type 1 was found in 121 (64.0%), type 2 in 23 (12.2%), type 3 in 36 (19.0%), type 4 in 3 (1.6%), type 5 in 2 (1.1%) and mixed infection in 3 (1.6%). There were no type 6 infections and one patient (0.5%) could not be typed. Genotype was not associated with diagnosis, age, or with HIV infection. Type 1 was associated with higher serum HCV RNA levels, and with a poor response to interferon. Progression to hepatic decompensation has been seen less frequently in those with type 3 compared to type 1 infection (p = 0.07). Three out of eleven patients studied over a longer time course showed a change in genotype, the remainder were persistently infected with HCV type 1. In conclusion, HCV genotype has clinical relevance in the management of haemophilic patients. Those with type 1 are probably more likely to develop serious liver disease and since they respond poorly to interferon-alpha, should be considered for new treatment strategies aimed at sustained clearance of HCV RNA.

Chronic Disease

Thalidomide as therapy for primary biliary cirrhosis: a double-blind placebo controlled pilot study.

Thalidomide has been reported to be effective in treating graft-versus-host disease, a condition with many clinical and pathological similarities to primary biliary cirrhosis. We performed a double-blind, placebo-controlled pilot study to assess the efficacy of thalidomide in 18 patients with biopsy-proven primary biliary cirrhosis (10 thalidomide, 8 placebo). Each patient was treated for 6 months and had a liver biopsy before and after treatment. Side effects, particularly sedation and fatigue, were more common on thalidomide and two patients were withdrawn from this group. There were no improvements in liver function tests or in liver histology, assessed morphometrically. A number of patients treated with thalidomide reported an improvement in pruritus. This study suggests that thalidomide is unlikely to be effective in altering the natural history of primary biliary cirrhosis.

Biopsy

The progression of HCV-associated liver disease in a cohort of haemophilic patients.

We have studied morbidity and mortality related to hepatitis C virus infection in haemophilic patients treated at our centre. 11/255 HCV seropositive patients have developed hepatic decompensation. 20 years after first exposure to lyophilized clotting factor concentrate the risk of hepatic decompensation is estimated to be 10.8% (95% CI 3.8-17.8%). There is a significantly increased risk associated with HIV infection, and also with increased age. For HIV seropositive patients the rates of decline in CD4 lymphocyte count and the development of p24 antigenaemia are significant risk factors for hepatic decompensation. Cirrhosis was seen in 9/19 HIV seropositive patients at post mortem. There was an association of cirrhosis with increased age but not with CD4 count, p24 antigenaemia, or AIDS. In conclusion, HCV infection is associated with serious liver disease in haemophilic patients, but so far this has been restricted to a minority of those at risk. HIV co-infection accelerates progression to hepatic decompensation, and we speculate that this is probably due to enhanced HCV replication in the presence of immune deficiency.

Adolescent