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Biomedical subjects

J A Scott

Publications and source records attributed to J A Scott.

At least 55 records · Page 3Linked to original sources

Contribution of nitric oxide synthases 1, 2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma.

Asthma is a chronic disease characterized by increased airway responsiveness and airway inflammation. The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in human asthma is controversial. To investigate the role of NO in an established model of allergic asthma, mice with targeted deletions of the three known isoforms of NOS (NOS1, 2, and 3) were studied. Although the inducible (NOS2) isoform was significantly upregulated in the lungs of ovalbumin (OVA)-sensitized and -challenged (OVA/OVA) wild-type (WT) mice and was undetectable in similarly treated NOS2-deficient mice, airway responsiveness was not significantly different between these groups. OVA/OVA endothelial (NOS3)-deficient mice were significantly more responsive to methacholine challenge compared with similarly treated NOS1 and NOS1&3-deficient mice. Airway responsiveness in OVA/OVA neuronal (NOS1)-deficient and neuronal/endothelial (NOS1&3) double-deficient mice was significantly less than that observed in similarly treated NOS2 and WT groups. These findings demonstrate an important function for the nNOS isoform in controlling the inducibility of airway hyperresponsiveness in this model of allergic asthma.

Animals↗

Prevalence of diabetic eye disease in an inner city population: the Liverpool Diabetic Eye Study.

PURPOSE: To measure the population prevalence of diabetic eye disease in an inner city setting. METHODS: As part of a systematic screening programme all adult diabetic patients in four general practices were invited to attend for slit-lamp biomicroscopy by a retinal specialist. Data on non-attenders were available from community-based photography. RESULTS: Of 395 diabetic patients identified, 326 attended biomicroscopy with photographic data available on a further 31, giving a 90% compliance rate. Point prevalence of diabetes in the target population was 12.4/ 1000. Demographic data included: mean age 60 years (range 13-92 years); type of control: type I 49, type II insulin-requiring (IR) 40, type II non-insulin-requiring (NIR) 268. Prevalences were as follows: any retinopathy: of all diabetic patients 33.6%, type I 36.7%, type II IR 45.0%, type II NIR 31.3%; proliferative/ advanced: all 1.1%, type I 2.0%, type II IR 0, type II NIR 1.1%; clinically significant macular oedema: all 6.4%, type I 2.3%, type II IR 16.2%, type II NIR 5.7%. The percentage of patients with retinopathy requiring follow-up by an opthalmologist was 4.5%, and 9.2% had macular exudates within 1 disc diameter of fixation or significant circinate maculopathy. Sight-threatening diabetic eye disease (STED) was found in 13.4%. A visual acuity of < or = 6/24 in the better eye occurred in 12 (3.4%) patients and of < or = 6/60 in the better eye in 3 (0.8%). CONCLUSIONS: Compared with previous population studies, prevalences appear to have declined in type I, but remain high in type II diabetic patients and especially in those requiring insulin.

Adolescent↗

Factors associated with the duration of breastfeeding amongst women in Perth, Australia.

Duration of breastfeeding was studied in 556 women delivering at 2 maternity hospitals in Perth, Australia. At discharge 83.8% of women were breastfeeding their infants, including 6% who were giving complementary feeds. At 3 and 6 months, 61.8% and 49.9%, respectively, were still breastfeeding. In a Cox survival analysis of factors associated with duration of breastfeeding a positive association was found with maternal education, age and intended duration of breastfeeding. Male infants were more likely to be weaned before female infants and women whose partners were unemployed, or did not have a preference for breastfeeding, breastfed for shorter duration. There is still a need for programmes which support and encourage breastfeeding, focusing particularly on younger, less well-educated women who intend to breastfeed for less than the recommended 4-6 months.

Adult↗

Diagnosis of pneumococcal pneumonia in epidemiological studies: evaluation in Kenyan adults of a serotype-specific urine latex agglutination assay.

A serotype-specific tube latex agglutination assay for 10 pneumococcal serotypes was evaluated with use of urine samples from 72 Kenyan adults with pneumonia whose blood or lung aspirate cultures were positive for Streptococcus pneumoniae, 203 patients with pneumonia whose cultures were negative for S. pneumoniae, and 101 afebrile controls. Detection thresholds for purified capsular polysaccharide in normal urine ranged from 0.33 to 10 ng/mL. The sensitivity of the assay for the 10 pneumococcal serotypes was 0.57 (95% confidence interval, 0.44-0.70) and was unaffected by human immunodeficiency virus seropositivity, prior antibiotic use, and bacteremic or nonbacteremic status but varied significantly by serotype. Of the pneumococci obtained by culture, 81% were of serotypes (1, 4, 5, 6, 7, 9, 12, 14, 19, and 22) that were included in the antigen assay. Strong simultaneous agglutinations against two different serotypes were found in urine samples from two patients. The specificity of the assay was 0.98 (lower 95% confidence limit, 0.95). Subjective reading of agglutination results introduced variation in specificity that may be inapparent if not formally measured. The assay extended the diagnostic yield in pneumococcal pneumonia by a factor of 2.2 (from 54 diagnoses established by blood culture to 119 established by both methods) and may therefore prove useful in reducing the sample size of epidemiological studies of pneumococcal pneumonia in adults.

Adolescent↗

Selective in vivo inhibition of inducible nitric oxide synthase in a rat model of sepsis.

Elevated production of nitric oxide (NO) by the inducible NO synthase (type II, iNOS) may contribute to the vascular hyporesponsiveness and hemodynamic alterations associated with sepsis. Selective inhibition of this isoenzyme is a possible therapeutic intervention to correct these pathophysiological alterations. Aminoguanidine has been shown to be a selective iNOS inhibitor and to correct the endotoxin-mediated vascular hypocontractility in vitro. However, to date aminoguanidine has not been shown to selectively block iNOS activity in vivo. The in vivo effects of aminoguanidine were assessed in the cecal ligation and perforation model of sepsis in rats. Aminoguanidine (1.75-175 mg/kg) was administered to septic and sham-operated rats for 3 h before euthanasia and harvest of tissues. NOS activities were determined in the thoracic aorta and lung from these animals. Aminoguanidine (17.5 mg/kg) did not alter the mean arterial pressure; however, it did inhibit induced iNOS (but not constitutive NOS) activity in the lung and thoracic aorta from septic animals. Only the higher dose of aminoguanidine (175 mg/kg) was able to increase the mean arterial pressure in septic and sham-operated animals. Thus selective inhibition of iNOS in vivo with aminoguanidine is possible, but our data suggest that other mechanisms, in addition to iNOS induction, are responsible for the loss of vascular tone characteristic of sepsis.

Animals↗

Using artificial neural network analysis of global ventilation-perfusion scan morphometry as a diagnostic tool.

OBJECTIVE: The purpose of this study was to determine whether global statistical data from radionuclide ventilation-perfusion scans could predict the likelihood of pulmonary embolism. MATERIALS AND METHODS: Digital data were obtained from 161 patients undergoing both radionuclide ventilation-perfusion scanning and subsequent pulmonary angiography. Morphometric data characterizing whole-lung perfusion and ventilation parameters were input into artificial neural networks in an attempt to predict the likelihood of pulmonary embolism. RESULTS: The performance of artificial neural networks using only automated global region of interest-based data was superior to that of clinicians in predicting the likelihood of acute pulmonary embolism in patients with normal findings on chest radiographs with segmental or larger emboli (p < .005) and in patients with normal findings on chest radiographs and emboli of any size (p < .01). Network performance did not significantly differ from clinician performance in patients with abnormal findings on chest radiographs. CONCLUSION: The adjunctive use of artificial neural networks using only user-independent, standard image statistics can significantly improve accuracy in the diagnosis of pulmonary embolism in patients with normal findings on chest radiographs.

Humans↗

Factors associated with the initiation and duration of breastfeeding: a review of the literature.

Breastfeeding is promoted internationally as the preferred method of feeding for infants up to the age of four to six months. As a consequence there is much research interest in factors which may be predictors of breastfeeding. This paper presents a review of the recent literature identifying factors associated with the initiation and duration of breastfeeding among Western women. Attention was focused on studies which employed multivariate analysis of the data and breastfeeding initiation and duration were considered as two uniquely separate events. This review reveals that the associations between breastfeeding and many of the factors commonly investigated were not consistent. Many of the strong associations previously reported in univariate studies were not evident in more recent studies which employed multivariate analysis to control for covariates and potential confounders. While there was a strong and consistent association with demographic factors such as maternal age and level of education, there was a less consistent association with factors such as marital and socioeconomic status. Similarly, the previously reported univariate associations between breastfeeding and biomedical factors such as parity, method of delivery and infant health were less consistent in multivariate studies. However, a consistent negative association has been reported between maternal smoking habits and breastfeeding duration. More recent studies have investigated the association between breastfeeding and psychosocial factors. There is evidence to suggest that fathers play an important role in the breastfeeding decision and that intended duration is a strong predictor of actual duration. Despite the inconsistency of the reported associations, this review highlights the fact that breastfeeding is multifactorial in nature and future programs aimed at promoting breastfeeding must take this into consideration.

Attitude of Health Personnel↗

Polyclonal, nonspecific 111In-IgG scintigraphy in the evaluation of complicated osteomyelitis and septic arthritis.

BACKGROUND: In this investigation we tested the hypothesis that 111In-IgG scintigraphy can differentiate infectious from sterile inflammatory processes in patients with complicated osteomyelitis or septic arthritis. METHODS: A prospective university hospital based study was performed over 18 months. We studied 31 sites of suspected infection, in 25 adult patients, (age 18 to 74 years, 12 females and 13 males) referred with clinical presentations compatible with complicated osteomyelitis or septic arthritis and in whom proof of the infection was likely to be obtained. The clinical setting in these patients was previous trauma, recent surgery, peripheral vascular disease or adjacent soft tissue infection. Whole body scintigraphy was performed at 1-6, 18-24 and 42-48 hours after administration of 55 MBq of 111In-IgG and results were compared to radiographs, 99mTc-MDP skeletal scintigraphy, biopsy specimens (9 sites) or synovial fluid aspirates (4 sites) and clinical follow-up. RESULTS: Of the 31 sites evaluated, 68% (21/31) were interpreted as negative for abnormal tracer accumulation and 32% (10/31) were considered positive. In patients who underwent biopsy and/or synovial fluid aspiration, 6 of 7 sites were correctly interpreted as positive; sensitivity 86%. Five of 6 sites were correctly interpreted as negative; specificity 83%. When all patients were considered using clinical follow-up in addition to culture results, 9 of 10 sites were correctly interpreted as positive (sensitivity 90%) and 20 of 21 patients were correctly interpreted as negative (specificity 95%). CONCLUSIONS: 111In-IgG scintigraphy is useful for detection of musculoskeletal infection in patients in whom sterile inflammatory events simulate infectious processes.

Adolescent↗

Nonadrenergic noncholinergic vasodilation of guinea pig pulmonary arteries is mediated by nitric oxide.

Nonadrenergic noncholinergic (NANC) mediated vasodilation may contribute to the maintenance of low pulmonary vascular tone. The NANC neurotransmitters, nitric oxide (NO) and the sensory neuropeptides, substance P and calcitonin gene related peptide (CGRP), were investigated as possible mediators of NANC vasodilation in guinea pig pulmonary arteries. Fresh guinea pig pulmonary artery rings, with and without an intact endothelium, were mounted in organ baths containing Krebs solution and precontracted with the prostaglandin F2alpha analogue U44069. In both endothelium-intact and denuded vessels, electrical field stimulation (1-12 Hz) in the presence of guanethidine and atropine resulted in a frequency-dependent vasodilation. The peptide fragment hCGRP8-37, a competitive antagonist of the CGRP receptors, the peptide fragment NK1 antagonist SP4-11, and the nonpeptide NK1 antagonist RP67580 had no effect on NANC vasodilation. In both endothelium-intact and denuded vessels, N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, inhibited NANC vasodilation, an effect that was reversible with L-arginine. We conclude that NANC vasodilation in guinea pig pulmonary arteries is mediated predominantly through NO activity.

Animals↗

Inhibitory effect of selenomethionine on the growth of three selected human tumor cell lines.

Selenium supplementation has been shown for many years to work as an anticarcinogenic agent both in epidemiology and in in vitro studies. Selenium supplementation has recently been shown to decrease total cancer incidence. However, the mechanism of action of selenium as an anticarcinogenic agent has yet to be elucidated. Selenomethionine was the predominant form of selenium in the dietary supplement in the study by Clark et al. (Clark, L.C., Combs, G.F., Turnbull, W.B., Slate, E.H., Chalker, D.K., Chow, J., Davis, L.S., Glover, R.A., Graham, G.F., Gross, E.G., Krongrad, A., Lesher, J.L., Park, H.K., Sanders, B.B., Smith, C.L., Taylor, J.R. and The Nutritional Prevention of Cancer Study Group (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. J. Am. Med. Assoc., 276 (24), 1957-1963) and therefore we evaluated the growth inhibitory effects of selenomethionine against human tumor cells. Selenomethionine was tested against each of three human tumor cell lines (MCF-7/S breast carcinoma, DU-145 prostate cancer cells and UACC-375 melanoma) and against normal human diploid fibroblasts. All cell lines demonstrated a dose-dependent manner of growth inhibition by selenomethionine. Selenomethionine inhibited the growth of all of the human tumor cell lines in the micromolar (microM) range (ranging from 45 to 130 microM) while growth inhibition of normal diploid fibroblasts required 1 mM selenomethionine, approximately 1000-fold higher than for the cancer cell lines. In short, normal diploid fibroblasts were less sensitive than the cancer cell lines to the growth inhibitory effects of selenomethionine. Furthermore, we show that selenomethionine administration to these cancer cell lines results in apoptotic cell death and aberrant mitoses. These results demonstrate the differential sensitivity of tumor cells and normal cells to selenomethionine.

Antineoplastic Agents↗

Favorable prognosis for children with Pfeiffer syndrome types 2 and 3: implications for classification.

Pfeiffer syndrome (PS) is an autosomal dominant condition comprising bilateral coronal craniosynostosis, midface hypoplasia with a beaked nasal tip, and broad and medially deviated thumbs and great toes. It is a clinically variable disorder and has been divided into three subtypes [Cohen, 1993: Am J Med Genet 45:300-307]. Type 1 represents the less severe cases, while types 2 and 3 are the more severe cases. These latter types tend to have a higher risk for neurodevelopmental problems and a reduced life expectancy. Here we review the clinical course of seven children with PS type 3. All of these children had severe manifestations of PS; however, development was essentially normal in three, mild delay was noted in two, and moderate delay in one. Favorable outcomes in children with types 2 and 3 PS were also documented by Moore et al. [1995: Cleft Pal-Craniofac J 32:62-70]. These cases illustrate that while children with PS types 2 and 3 have an increased risk for neurodevelopmental difficulties, a favorable outcome can be achieved in some cases with aggressive medical and surgical management. Finally, although such management should be the rule for PS types 2 and 3, it needs to be remembered that normal outcome is not the rule. The prognosis for favorable neurodevelopmental outcome and/or life expectancy remains guarded in most cases.

Acrocephalosyndactylia↗

Deletion 22q11: a newly recognized cause of behavioral and psychiatric disorders.

BACKGROUND: Chromosome 22q11 deletion (del22q11), the most common microdeletion syndrome, causes a wide spectrum of clinical disorders. Recent studies have suggested that significant psychiatric and behavioral disturbances occur in up to 60% of these individuals. OBJECTIVE: To illustrate the spectrum of behavioral and psychiatric abnormalities associated with del22q11 and the subtle nature of its associated physical findings. PATIENTS AND METHODS: Case series describing psychiatric and behavioral findings in 3 patients with del22q11. RESULTS AND CONCLUSIONS: Behavioral and psychiatric problems are common in patients with del22q11 syndrome. Because the physical manifestations of the disorder are so variable and may be subtle, the behavioral and psychiatric manifestations may be the presenting problem. Providers must therefore consider del22q11 as a potential diagnosis in children and adults with behavioral and psychiatric problems. Furthermore, behavioral and psychiatric problems need to be looked for when caring for children and adolescents with a known diagnosis of del22q11.

Adolescent↗

Stickler syndrome without eye involvement is caused by mutations in COL11A2, the gene encoding the alpha2(XI) chain of type XI collagen.

Eye involvement has been considered a principal component feature in Stickler syndrome. However, families lacking eye involvement have been reported. We describe such a family and show that their phenotype is due to a heterozygous 27 basepair deletion in the gene COL11A2, which encodes the alpha2(XI) chain of type XI collagen. This is the second family in whom a COL11A2 mutation has been found to cause Stickler syndrome without eye involvement. This result confirms the role of COL11A2 in the etiopathogenesis of this disorder.

Child, Preschool↗

Serotype distribution and prevalence of resistance to benzylpenicillin in three representative populations of Streptococcus pneumoniae isolates from the coast of Kenya.

As surveillance data from sub-Saharan Africa are few, three representative populations of Streptococcus pneumoniae isolates were examined in Kenya for serotype distribution and Etest minimum inhibitory concentrations (MICs) of benzylpenicillin: (1) 75 lung aspirate or blood culture isolates from 301 consecutive adult patients with pneumonia, (2) 112 invasive isolates from continuous pediatric inpatient surveillance over 4 years, and (3) 97 nasopharyngeal isolates from systematically selected sick children. The proportions with benzylpenicillin MICs of > or = 0.1 microgram/mL were 0.27, 0.29, and 0.47, respectively. Vaccine-related serotypes accounted for 96% of invasive isolates from children and 90% of those from human immunodeficiency virus (HIV)-seropositive adults. Serotype 1 accounted for 44% of pneumococci from HIV-seronegative patients but only 5% of those from HIV-seropositive patients (P = .0002). Of serotype 1 isolates, 98% were susceptible to benzylpenicillin, but serogroups 13, 14, 19, and 23 were strongly associated with an MIC of > or = 0.1 microgram/mL.

Adult↗