Why journals should not publish articles funded by the tobacco industry.
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Biomedical Research↗
Biomedical subjects
J King
Publications and source records attributed to J King.
Competition among Streptococcus pneumoniae for intranasal colonization in a mouse model.
Widespread use of conjugate vaccines against Streptococcus pneumoniae, by reducing carriage of S. pneumoniae serotypes included in the vaccine, may result in an increase in nasopharyngeal carriage of - and disease from - nonvaccine serotypes of the same species. Mathematical models predict that the extent of such replacement will depend positively on the degree to which carriage of vaccine-type S. pneumoniae inhibits acquisition of nonvaccine-type pneumococci, and may depend negatively on the inhibition of vaccine-type pneumococci by nonvaccine-type pneumococci. We used a mouse model of intranasal carriage of pneumococci to test whether such inhibition occurs between different pneumococcal strains. Mice carrying a streptomycin-resistant derivative of S. pneumoniae BG9163 (serotype 6B) as a resident strain showed reduced levels of colonization when challenged intranasally by optochin-resistant derivatives of the same strain and of a serotype 23F pneumococcus, BG8826. Inhibition could be overcome by increasing the dose of the challenge strain. Carriage of optochin-resistant BG9163 did not inhibit acquisition of the streptomycin-resistant variant. Colonization by a challenge strain did not significantly affect the level of colonization with the resident strain. These results provide evidence that is consistent with several hitherto untested assumptions of mathematical models of serotype replacement and suggest that a biological mechanism exists that could account for serotype replacement that is observed in clinical trials. The findings provide a basis for further studies of in vivo interactions between strains of S. pneumoniae.
Animals↗
Visualization of the maturation transition in bacteriophage P22 by electron cryomicroscopy.
Large-scale conformational transitions are involved in the life-cycle of many types of virus. The dsDNA phages, herpesviruses, and adenoviruses must undergo a maturation transition in the course of DNA packaging to convert a scaffolding-containing precursor capsid to the DNA-containing mature virion. This conformational transition converts the procapsid, which is smaller, rounder, and displays a distinctive skewing of the hexameric capsomeres, to the mature virion, which is larger and more angular, with regular hexons. We have used electron cryomicroscopy and image reconstruction to obtain 15 A structures of both bacteriophage P22 procapsids and mature phage. The maturation transition from the procapsid to the phage results in several changes in both the conformations of the individual coat protein subunits and the interactions between neighboring subunits. The most extensive conformational transformation among these is the outward movement of the trimer clusters present at all strict and local 3-fold axes on the procapsid inner surface. As the trimer tips are the sites of scaffolding binding, this helps to explain the role of scaffolding protein in regulating assembly and maturation. We also observe DNA within the capsid packed in a manner consistent with the spool model. These structures allow us to suggest how the binding interactions of scaffolding and DNA with the coat shell may act to control the packaging of the DNA into the expanding procapsids.
Bacteriophage P22↗
Treatment of schizophrenia. What in fact is schizophrenia?
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Diagnosis, Differential↗
Comparison of visual--vestibular interaction in insulin-dependent and non-insulin-dependent diabetes mellitus.
We compared various measures of visual-vestibular interaction in subjects with insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM), as well as non-diabetic controls. Subjects with IDDM exhibited significantly greater postural sway than controls on those conditions in the Clinical Test of Sensory Interaction and Balance (CTSIB) which require greater reliance on the vestibular system (p < 0.005). The IDDM group also exhibited significantly worse gaze-holding in darkness and a significantly higher mean slow phase eye velocity (SPV) of optokinetic nystagmus (OKN; p<0.05 for both comparisons). However, there were no significant differences in latency to circularvection (CV). The NIDDM group showed a significant increase in postural sway across all 12 conditions compared with the controls, as well as a significant decrease in gaze-holding in darkness (p < 0.05 and p < 0.0005, respectively). However, they showed no significant difference in OKN SPV and a significant decrease in latency to CV for anticlockwise trials only (p < 0.05). These results suggest that IDDM and NIDDM are both associated with specific but different changes in visual-vestibular interaction.
Adult↗
The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infection.
Pneumococcal proteins, alone, in combination with each other, or in combination with capsular polysaccharide-protein conjugates may be useful pneumococcal vaccine components. Four proteins with a potential for use in vaccines are PspA, pneumolysin, PsaA, and PspC. In a mouse model of carriage, PsaA and PspC were the most efficacious vaccine proteins. Of these, PsaA was the best at eliciting protection against carriage. However, a combination of PspA and pneumolysin may elicit stronger immunity to pulmonary infection and possibly sepsis than either protein alone. Recently, a phase one trial of a recombinant family 1 PspA was completed in man. PspA was observed to be safe and immunogenic. Injection of 0.1 ml of immune serum diluted to 1/400 was able to protect mice from fatal infection with S. pneumoniae. Under these conditions, pre-immune serum was not protective. The immune human serum protected mice from infections with pneumococci expressing either of the major PspA families (1 and 2) and both of the pneumococcal capsular types tested: 3 and 6.
Adult↗
Echogenicity of liver metastases is an independent prognostic factor after potentially curative treatment.
HYPOTHESIS: Intraoperative echogenic appearance of liver metastases from colorectal cancer is a prognostic factor of outcome after curative treatment. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Department of Surgery at a university hospital. PATIENTS: One hundred forty-three consecutive patients with hepatic metastases from colorectal cancer who underwent liver resection with curative intent between 1992 and 1998. INTERVENTION: Curative treatment was achieved by liver resection alone, liver resection plus edge cryotherapy, or liver resection plus cryotherapy to lesions not amenable to further resection. In patients with more than 2 lesions, a hepatic artery catheter was placed for regional chemotherapy. MAIN OUTCOME MEASURES: The echogenic appearance of the liver metastases was assessed by intraoperative ultrasound by a single person throughout the study using a 5-MHz ultrasound probe. The findings were prospectively entered into the database. RESULTS: Fifty-four percent of patients had hyperechoic metastases. This group had significantly longer overall (log rank, P<.001) and recurrence-free survival (log rank, P =.004) compared with patients who had hypoechoic metastases (36%). A significantly higher percentage of mucin-secreting tumors were found in the hypoechoic patient group (chi(2), P =.001). Dukes stage of the primary tumor (P =.02), echogenicity of the liver secondaries (P =.04), and diameter of the largest resected metastasis (P =.01) were independent prognostic factors for recurrence-free survival in the Cox regression model. CONCLUSION: These results support the hypothesis that echogenicity of liver metastases from colorectal cancer is an independent prognostic factor of outcome after curative resection.
Colorectal Neoplasms↗
Predictive value of the ultrasensitive HIV viral load assay in clinical practice.
The aim of this study was to determine whether an HIV viral load of <50 copies/ml (c/ml), in the first available plasma sample to have shown a viral load of <400 c/ml, in patients on antiretroviral therapy, is correlated with longer term suppression of viral load (at <400 c/ml) compared to a viral load of 50-399 c/ml, and secondly, to compare the results obtained by ultrasensitive and standard viral load assays carried out on the same sample. A total of 98 HIV-positive patients on antiretroviral therapy with a viral load of <400 c/ml and at least one subsequent viral load measurement, were selected. For each patient, the first available specimen showing a viral load of <400 c/ml was tested using the Roche Amplicor ultrasensitive viral load assay, and patients were followed up subsequently for a median period of 52 weeks. Whether patients achieved an ultrasensitive viral load (USVL) of <50 c/ml or not made very little difference to the proportion of patients in each group showing continued response to treatment (52% vs. 45% respectively). The only variable that was shown to significantly predict longevity of response was the number of antiretroviral drugs used. Secondly, a standard viral load of <400 c/ml but with a detectable signal above background levels, was strongly predictive of a USVL of >50 c/ml. Overall, the findings suggest that the advantage in predictive value of the ultrasensitive over the standard HIV viral load assay, shown previously in clinical trials, may be limited in clinical practice.
Anti-HIV Agents↗
Antibiotics for preterm labour with intact membranes.
BACKGROUND: There may be a link between infection and preterm birth. OBJECTIVES: Since rupture of the membranes is an important factor in the progression of preterm labour, it is important to see if antibiotics are of any benefit prior to membrane rupture. The objective of this review was to assess the effects of antibiotics administered to women in preterm labour with intact membranes, on maternal and neonatal outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and reference lists of articles. We contacted experts in the field. SELECTION CRITERIA: Randomised trials which compared antibiotic treatment with placebo or no treatment for women in preterm labour (between 20 and 36 weeks gestation) with intact membranes. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for missing data. MAIN RESULTS: Meta-analysis of the ten included trials demonstrated a statistically significant prolongation of pregnancy associated with the use of antibiotics (5. 4 days, 95% confidence interval (CI) 0.9- 9.8 days). Antibiotic treatment was also associated with a statistically significant reduction in maternal infection (odds ratio (OR) 0.59, 95% CI 0.36, 0.97) and neonatal necrotising enterocolitis (OR 0.33, 95% CI 0.13, 0.88). No statistically significant effect was detected on the neonatal outcomes of respiratory distress syndrome and neonatal sepsis, although there was a trend towards the latter (OR 0.67, 95% CI 0.42, 1.07). An increase in perinatal mortality was observed in the group receiving antibiotics (OR 3.36, 95% CI 1.21, 9.32). REVIEWER'S CONCLUSIONS: Although a prolongation in time to delivery and a trend towards a reduction in neonatal sepsis was detected, this review fails to demonstrate a clear overall benefit from antibiotic treatment for preterm labour with intact membranes on neonatal outcomes and raises concerns about increased perinatal mortality for those who received antibiotics. This treatment cannot therefore be currently recommended for routine practice. Further research is required to identify a subgroup of women (and their babies) who are more likely to experience benefit from antibiotic treatment for preterm labour prior to membrane rupture, and to identify which antibiotic or combination of antibiotics is most effective. The results of the ongoing ORACLE trial should help resolve some of the uncertainties revealed by this review.
Anti-Bacterial Agents↗
H2-antagonists in the treatment of colon and breast cancer.
Several clinical trials have now been carried out with histamine type 2 receptor antagonists in cancer patients often as an adjunct to surgical resection of the primary tumour While promising results have been obtained in some groups of patients with gastrointestinal cancer, with increased survival and evidence of increased immunological recognition of tumour, results are less encouraging for breast cancer. This may be due to differences in the levels of histamine or the role of histamine in growth of these different tumour types.
Adjuvants, Immunologic↗
Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.
OBJECTIVE: To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine. STUDY DESIGN: A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions. RESULTS: In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group. CONCLUSIONS: This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza.
Administration, Intranasal↗
Beneficial effects of increasing monounsaturated fat intake in adolescents with type 1 diabetes.
This study aimed to increase the monounsaturated fat content in the diet of outpatient adolescents with type 1 diabetes and to examine the metabolic effects after 12 weeks. Twenty-three adolescents were randomly allocated to either a high monounsaturated fat diet or a control diet. Their mean age was 16.9 (S.D. 2.1) years and median HbA(1c) was 9.1% [IQR 7.9-10.4%]. Dietary targets were not reached judged by their 4-day food diaries. However, the whole study group had a significant increase in monounsaturated fat as indexed by red cell phospholipid fatty acids (RCFAs), with an increase of n-9 RCFAs from 14.9% [IQR: 14.5-21.7%] to 21.7% [IQR: 18.8-25.6%] (P=0.002). Changes in n-9 RCFAs were inversely related to changes in HbA(1c) (R(2)=0.26, P=0.02), such that a 10% increase in n-9 RCFAs corresponded to a 0.64% improvement (decrease) in HbA(1c). Changes in n-9 RCFAs were also inversely related to changes in plasma total cholesterol (R(2)=0.38, P=0.002) and plasma LDL cholesterol (R(2)=0. 21, P=0.03). These changes were not associated with changes in insulin dose, body weight or physical activity. Overall, the results demonstrate that a modest increase in the monounsaturated fat content of an adolescent diet has the potential to improve glycaemic control and lipid profile.
Adolescent↗
Screening for preclinical type 1 diabetes in a discrete population with an apparent increased disease incidence.
Environmental agents are proposed to play a role in triggering or exacerbating pancreatic islet autoimmunity in people genetically predisposed to type 1 diabetes. However, with few exceptions, these agents remain enigmatic. Clues to environmental agents may be found by investigating population/geographic clusters or 'hotspots' of high disease incidence. We were alerted to a small community where the incidence of type 1 diabetes appeared to be five-fold higher than expected. Because type 1 diabetes is now recognized to have a subclinical phase during which anti-islet antibodies can be detected, we aimed to identify and characterize a reservoir of children with subclinical disease in this community. Venous blood samples were collected from 1906/2347 (81%) local school children during one week. Islet cell antibodies (ICAs) were detected in 122 (6.4%) children, 18 (0.9%) being high titer (> or = 20 Juvenile Diabetes Foundation units (JDFu)). On retest, 15 months later, the majority of low titer ICAs were undetectable, whereas high-titer ICAs persisted. The latter were found in two distinct age-related, ethnically similar groups. The younger group, aged 6-9 yr, had antibodies to insulin (IAAs), glutamic acid decarboxylase (GAD) and tyrosine phosphatase IA2 in addition to ICA, human leukocyte antigen (HLA) genes associated with susceptibility to type 1 diabetes, and lower first-phase insulin responses (FPIRs) to intravenous glucose. The older group, aged 13-16 yr, the age cohort of the index clinical cases, had few antibodies other than ICA, non-susceptibility HLA genes and normal FPIRs. During follow-up, three children, all from the younger group with multiple antibodies and FPIRs less than the first percentile, developed diabetes 4, 6 and 7 yr after screening. The finding of two age groups of subclinical disease suggests that if environmental agents triggered islet autoimmunity they did not act constantly on the community. Furthermore, the absence of multiple autoantibodies and/or HLA susceptibility genes in the older group, the source of index clinical cases, implies they are a residual subgroup with slow or absent progressive beta-cell destruction. This study illustrates that the natural history of type 1 diabetes may be elucidated by analyzing age-related subclinical disease in the general population.
Journal Article↗
Correction of lunate malalignment when bone grafting scaphoid nonunion with humpback deformity: rationale and results of a technique revisited.
Patients with scaphoid nonunion with humpback deformity and collapse of the wrist were treated with palmar wedge bone grafting combined with reduction of the lunate to correct the dorsal intercalated segment instability deformity. Union was obtained at an average of 3 months, and patient satisfaction with functional outcome and pain relief was high. Palmar wedge bone grafting combined with correction of lunate malalignment successfully achieved scaphoid union, restored scaphoid length, and avoided the potential complication of scaphoid malunion. This report revisits a technique that facilitates accurate correction of lunate malalignment (dorsal intercalated segment instability) by initial reduction and pin fixation to the radius before insertion of scaphoid bone graft and internal fixation.
Adolescent↗
Histamine, mast cells and tumour cell proliferation in breast cancer: does preoperative cimetidine administration have an effect?
Endogenous histamine has been shown to effect growth mechanisms in experimental mammary carcinomas via H2 membrane receptors (Cricco et al, 1994). Both H1 and H2 binding sites are present in human mammary glands but only 75% malignant carcinomas express H2 receptors (Lemos et al, 1995). The presence of mast cells around tumour tissue raises questions concerning the source of histamine in breast tumour tissue. While cimetidine, an H2 antagonist, has been shown to influence the presence of tumour infiltrating lymphocytes (TIL) in colorectal cancer (Adams and Morris, 1994, 1997) that was not found to be the case in breast cancer (Ng et al, 1995). In recent studies tumour cell proliferation, as measured by Ki-67 antibody labelling, has been seen as an additional prognostic indicator in breast cancer (Railo et al, 1993, 1997; Ferno, 1998; Schauer et al, 1998). We investigated the possibility that cimetidine may influence tumour proliferation by blocking the growth-promoting effects of histamine. No relationship between preoperative cimetidine administration and tumour cell proliferation was seen overall. A weak correlation was seen between tissue histamine content and mast cell count which was not influenced by cimetidine. Tumour cell proliferation correlated well with other prognostic indicators such as grade and differentiation.
Adult↗
The use of intra-aortic counterpulsation balloon for the treatment of cerebral vasospasm and edema.
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Aneurysm, Ruptured↗
Characteristics of a rural geriatric rehabilitation service.
The aim of this article is to examine the role of two geriatric rehabilitation units in a large rural area, and compare them with published data about rehabilitation units in urban settings. We look at the inputs to the units and the measurable outputs, including length of stay, discharge disposition of patients and changes in patient activities of daily living. We show that rehabilitation services provided in the rural environment have lengths of stay and improvements in activities of daily living that are similar to those found in urban areas.
Aged↗
Correlates of immune protection induced by live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine.
The authors conducted a 2-year, multicenter, double-blind, placebo-controlled efficacy field trial of live, attenuated, cold-adapted, trivalent influenza vaccine administered by nasal spray to children 15-71 months old. Overall, vaccine was 92% efficacious at preventing culture-confirmed infection by influenza A/H3N2 and influenza B. Because influenza A/H1N1 did not cause disease during the years in which this study was conducted, the authors sought to determine vaccine efficacy and correlates of immune protection against experimental challenge with 107 TCID50 of attenuated H1N1 (vaccine strain) by intranasal spray. Prechallenge assessments included serum hemaglutination-inhibiting (HAI) antibody and nasal wash IgA antibody to H1N1. Vaccine was 83% efficacious (95% confidence interval, 60%-93%) at preventing shedding of H1N1 virus after challenge. Any serum HAI antibody or any nasal wash IgA antibody was correlated with significant protection from H1N1 infection as indicated by vaccine-virus shedding, and high efficacy against H1N1 challenge was demonstrated.
Administration, Intranasal↗