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1.  Persistence, adherence, and toxicity with oral CMF in older women with early-stage breast cancer (Adherence Companion Study 60104 for CALGB 49907) 
Annals of Oncology  2012;23(12):3075-3081.
Background
Cyclophosphamide-methotrexate-5-fluorouracil (CMF) is often selected as adjuvant chemotherapy for older patients with early-stage breast cancer due to perceived superior tolerability. We sought to measure persistence with CMF, adherence to oral cyclophosphamide, and the association of these with toxic effects.
Patients and methods
CALGB 49907 was a randomized trial comparing standard chemotherapy (CMF or AC, provider/patient choice) with capecitabine in patients aged ≥65 with stage I–IIIB breast cancer. Those randomized to standard therapy and choosing CMF were prescribed oral cyclophosphamide 100 mg/m2 for 14 consecutive days in six 28-day cycles. Persistence was defined as being prescribed six cycles of at least one of the three CMF drugs. Adherence was the number of cyclophosphamide doses that women reported they had taken divided by the number prescribed. Persistence and adherence were based on case report forms and medication calendars.
Results
Of 317 randomized to standard chemotherapy, 133 received CMF. Median age was 73 (range 65–88). Seventy-one percent submitted at least one medication calendar; 65% persisted with CMF. Non-persistence was associated with node negativity (P = 0.019), febrile neutropenia (P = 0.002), and fatigue (P = 0.044). Average adherence was 97% during prescribed cycles.
Conclusions
Self-reported adherence to cyclophosphamide was high, but persistence was lower, which may be attributable to toxic effects.
doi:10.1093/annonc/mds133
PMCID: PMC3501229  PMID: 22767584
antineoplastic combined chemotherapy protocols; breast neoplasms; geriatrics; medication adherence; patient compliance; toxicity
2.  Paclitaxel efficacy and toxicity in older women with metastatic breast cancer: combined analysis of CALGB 9342 and 9840 
Annals of Oncology  2011;23(3):632-638.
Background:
Two Cancer and Leukemia Group B (CALGB) studies were utilized to determine the efficacy and tolerability of paclitaxel (Taxol) in older patients with metastatic breast cancer.
Patients and methods:
CALGB 9840 evaluated weekly paclitaxel (80 mg/m2) versus paclitaxel every 3 weeks (175 mg/m2); CALGB 9342 evaluated three doses of paclitaxel as follows: 175, 210 and 250 mg/m2 each over 3 h every 3 weeks. Of the 1048 patients, paclitaxel was used first line in 57%. The groups: (i) <55 years (45%), (ii) 55–64 years (29%), and (iii) ≥65 years (26%).
Results:
Tumor response was also similar among age groups. First-line therapy (P = 0.0001) and better performance status (PS) (P = 0.018) were significantly related to higher response. Age did not significantly relate to overall survival (OS) or progression-free survival (PFS). First-line therapy, better PS, estrogen receptor positive status and a fewer number of metastatic sites were significantly related to improved OS and PFS. The grade ≥3 toxic effects that increased linearly with age were leucopenia (P = 0.0099), granulocytopenia (P = 0.022), anorexia (P = 0.028), bilirubin elevation (P = 0.0035) and neurotoxicity (P < 0.0001). Patients over 65 years receiving second-line therapy had the shortest time to neurotoxicity.
Conclusions:
Older women with breast cancer derive similar efficacy from treatment with paclitaxel as younger women. Older women are at increased risk for specific toxic effects.
doi:10.1093/annonc/mdr297
PMCID: PMC3331731  PMID: 21693770
breast cancer; elderly; geriatric oncology; geriatrics; neurotoxicity; paclitaxel
3.  Spikes alone do not behavior make: Why neuroscience needs biomechanics 
Current opinion in neurobiology  2011;21(5):816-822.
Neural circuits do not function in isolation; they interact with the physical world, accepting sensory inputs and producing outputs via muscles. Since both these pathways are constrained by physics, the activity of neural circuits can only be understood by considering biomechanics of muscles, bodies, and the exterior world. We discuss how animal bodies have natural stable motions that require relatively little activation or control from the nervous system. The nervous system can substantially alter these motions, by subtly changing mechanical properties such as leg sti ness. Mechanics can also provide robustness to perturbations without sensory reflexes. By considering a complete neuromechanical system, neuroscientists and biomechanicians together can provide a more integrated view of neural circuitry and behavior.
doi:10.1016/j.conb.2011.05.017
PMCID: PMC3183174  PMID: 21683575
biomechanics; neuromechanics; preflexes; reflexes; resonance; stability
4.  Post-traumatic anxiety associates with failure of the innate immune receptor TLR9 to evade the pro-inflammatory NFκB pathway 
Translational Psychiatry  2012;2(2):e78-.
Post-traumatic anxiety notably involves inflammation, but its causes and functional significance are yet unclear. Here, we report that failure of the innate immune system Toll-like receptor 9 (TLR9) to limit inflammation is causally involved with anxiety-associated inflammation and that peripheral administration of specific oligonucleotide activators of TLR9 may prevent post-traumatic consequences in stressed mice. Suggesting involvement of NFκB-mediated enhancement of inflammatory reactions in the post-traumatic phenotype, we found association of serum interleukin-1β increases with symptoms severity and volumetric brain changes in post-traumatic stress disorder patients. In predator scent-stressed mice, the moderate NFκB-activating oligonucleotides mEN101 and its human ortholog BL-7040, but not the canonic NFκB activator oligonucleotide ODN1826, induced anxiolytic effects. In stressed mice, peripherally administered mEN101 prevented delayed stress-inducible serum interleukin-1β increases while limiting stress-characteristic hippocampal transcript modifications and the anxiety-induced EGR1-mediated neuronal activation. Attesting to the TLR9 specificity of this response, BL-7040 suppressed NFκB-mediated luciferase in transfected cells co-expressing TLR9, but not other TLRs. Furthermore, TLR9−/− mice were mEN101 and BL-7040 resistant and presented unprovoked anxiety-like behavior and anxiety-characteristic hippocampal transcripts. Our findings demonstrate functional relevance of TLR9 in protecting stressed mammals from overreacting to traumatic experiences and suggest using oligonucleotide-mediated peripheral TLR9 activation to potentiate the innate immune system and prevent post-traumatic inflammation and anxiety.
doi:10.1038/tp.2012.4
PMCID: PMC3309554  PMID: 22832815
inflammation; innate immune system; NFκB; oligonucleotide; post-traumatic stress; TLR9
5.  Frequency of Sinus Disease in Normal Subjects and Patients with Benign Paroxysmal Positional Vertigo 
Background/Aims
To determine if patients with benign paroxysmal positional vertigo (BPPV) have a higher frequency of rhinosinusitis than people with normal vestibular function.
Methods
The subjects were 52 patients with BPPV and 46 normal people. Every subject had a sinus CT scan, a blood draw for IgE and a rhinologic examination by an otolaryngologist.
Results
The frequency of rhinosinusitis based on physician diagnosis was 49% and based on CT scan findings 59%. This difference approached significance (p = 0.08). The observed frequency of rhinosinusitis was higher than predicted by survey data about the southern US region. The data trended toward higher prevalence of rhinosinusitis (by physician diagnosis) in the BPPV patients versus controls (58 vs. 39%, p = 0.06).
Conclusion
BPPV patients have a higher frequency of sinus disease compared to people with normal vestibular systems, perhaps due to age differences, but physiologic factors may also be involved. The higher frequency of rhinosinusitis in this geographical area than reported rates based on survey data raises concerns about the usefulness of questionnaire data for estimating population prevalence.
doi:10.1159/000296304
PMCID: PMC3696370  PMID: 20424495
Benign paroxysmal positional vertigo; Public health; Rhinosinusitis; Sinus disease
6.  New epidemiological findings on benign paroxysmal positional vertigo 
Benign paroxysmal positional vertigo is associated with a range of factors, some previously unknown
doi:10.1136/jnnp.2006.109447
PMCID: PMC2117669  PMID: 17135453
8.  Self-monitoring of oral anticoagulation: does it work outside trial conditions? 
Journal of Clinical Pathology  2009;62(2):168-171.
Background:
Patient self-monitoring (PSM) of oral anticoagulation therapy (OAT) can improve anticoagulant control, but poor uptake and high dropout rates have prompted suggestions that PSM is suitable for only a minority of patients in the UK.
Aims:
To determine whether PSM could be a viable alternative to regular hospital anticoagulant clinic attendance, if offered from the start of treatment.
Methods:
318 consecutive patients referred, for the first time, to an anticoagulation clinic were assessed for eligibility using established criteria. Patients electing for PSM attended training and, following successful assessment, performed a capillary blood INR every two weeks or more frequently if directed to do so by the anticoagulation clinic. Primary outcome measures were uptake of PSM and the percentage time in target therapeutic INR range (TIR) compared to patients electing for routine clinic care.
Results:
Of 318 patients referred for OAT, 188 were eligible for PSM. 84 (26%) elected to self-monitor, of whom 72 (23%) remained self-monitoring or had completed their course of treatment at the end of the audit. Self-monitoring patients had significantly better anticoagulant control than those receiving routine hospital anticoagulation clinic care (TIR 71% vs 60%, p = 0.003) and significantly less time outside critical limits, ie, INR <1.5 or >5.0 (0.45% vs 2.04%, p = 0.008).
Conclusions:
Patients offered PSM from the start of treatment show increased uptake compared to previous UK studies and a level of oral anticoagulation control comparable to that reported in previous clinical trials.
doi:10.1136/jcp.2008.059634
PMCID: PMC2629005  PMID: 19181634
9.  Outdoor carbon monoxide, nitrogen dioxide, and sudden infant death syndrome 
Archives of Disease in Childhood  2005;90(7):750-753.
Methods: A total of 169 case and 169 matched control infants born between 1988 and 1992, were studied. CO and NO2 concentrations, averaged for all days within the infant's lifespan, and the last 30 days, 7 days, 3 days, and 1 day of life were obtained from air pollutant data provided by the California Air Resources Board.
Results: Based on monthly aggregated data, average CO and particularly NO2 were associated with SIDS count, even after adjustment for seasonal trends. SIDS outcome was not significantly associated with high average outdoor CO levels for any time period. However, high average outdoor NO2 levels on the last day of the infant's exposure period were significantly associated with SIDS; the adjusted odds ratio was 2.34 (95% CI 1.13 to 4.87).
Conclusions: SIDS may be related to high levels of acute outdoor NO2 exposure during the last day of life. Further studies are needed to replicate this finding.
doi:10.1136/adc.2004.057091
PMCID: PMC1720470  PMID: 15970620
10.  Primary local orbital amyloidosis: biochemical identification of the immunoglobulin light chain κIII subtype in a small formalin fixed, paraffin wax embedded tissue sample 
Journal of Clinical Pathology  2005;58(5):539-542.
Background: Amyloidosis refers to a heterogeneous group of disorders associated with the deposition of chemically distinct amyloid fibril proteins. Precise determination of chemical amyloid type has diagnostic, therapeutic, and prognostic relevance. Although immunohistochemical techniques are used routinely to determine the amyloid type, the results can be negative or inconclusive, so that biochemical characterisation is often required. The development and application of new biochemical microtechniques suitable for examination of extremely small tissue samples is essential for precise identification of the deposited amyloid proteins.
Aims: To investigate biochemically the amyloid proteins present in a formalin fixed paraffin wax embedded orbital tissue from a patient with localised orbital amyloidosis in whom immunohistochemistry was not helpful in the determination of amyloid type.
Methods: Extraction of amyloid proteins from fixed tissue and their identification was carried out by a recently developed microtechnique. An extremely small tissue sample was dewaxed and extracted with formic acid. The extracted material was analysed using electrophoresis, western blotting, and amino acid sequencing.
Results: Biochemical examination of the extracted proteins showed the presence of immunoglobulin (Ig) derived amyloid proteins, which were composed of the N-terminal fragments of the Ig light chain κIII subtype (AL-κIII) (16, 8, and 3 kDa).
Conclusions: This is the first chemically proved AL case reported in association with primary localised orbital amyloidosis. The biochemical microtechnique used was useful in achieving a precise diagnosis of amyloid disease, in a case where the results of routine immunohistochemical examination of amyloid were inconclusive.
doi:10.1136/jcp.2004.022517
PMCID: PMC1770653  PMID: 15858128
immunoglobulin light chains; microtechnique; orbital amyloidosis
11.  Secondary prevention of coronary heart disease in South Wales: a survey following myocardial infarction 
Heart  2004;90(11):1332-1333.
doi:10.1136/hrt.2003.010942
PMCID: PMC1768521  PMID: 15486137
myocardial infarction; secondary prevention; coronary heart disease
12.  Atypical giant cell arteritis resulting in arm amputation. 
doi:10.1308/003588403766274980
PMCID: PMC1964395  PMID: 12855030
13.  Heterogeneity of gastric histology and function in food cobalamin malabsorption: absence of atrophic gastritis and achlorhydria in some patients with severe malabsorption 
Gut  2000;47(5):638-645.
BACKGROUND—The common but incompletely understood entity of malabsorption of food bound cobalamin is generally presumed to arise from gastritis and/or achlorhydria.
AIM—To conduct a systematic comparative examination of gastric histology and function.
SUBJECTS—Nineteen volunteers, either healthy or with low cobalamin levels, were prospectively studied without prior knowledge of their absorption or gastric status.
METHODS—All subjects underwent prospective assessment of food cobalamin absorption by the egg yolk cobalamin absorption test, endoscopy, histological grading of biopsies from six gastric sites, measurement of gastric secretory function, assay for serum gastrin and antiparietal cell antibodies, and direct tests for Helicobacter pylori infection.
RESULTS—The six subjects with severe malabsorption (group I) had worse histological scores overall and lower acid and pepsin secretion than the eight subjects with normal absorption (group III) or the five subjects with mild malabsorption (group II). However, histological findings, and acid and pepsin secretion overlapped considerably between individual subjects in group I and group III. Two distinct subgroups of three subjects each emerged within group I. One subgroup (IA) had severe gastric atrophy and achlorhydria. The other subgroup (IB) had little atrophy and only mild hypochlorhydria; the gastric findings were indistinguishable from those in many subjects with normal absorption. Absorption improved in the two subjects in subgroup IB and in one subject in group II who received antibiotics, along with evidence of clearing of H pylori. None of the subjects in group IA responded to antibiotics.
CONCLUSIONS—Food cobalamin malabsorption arises in at least two different gastric settings, one of which involves neither gastric atrophy nor achlorhydria. Malabsorption can respond to antibiotics, but only in some patients. Food cobalamin malabsorption is not always synonymous with atrophic gastritis and achlorhydria, and hypochlorhydria does not always guarantee food cobalamin malabsorption.


Keywords: cobalamin; cobalamin malabsorption; atrophic gastritis; achlorhydria; pepsin; gastrin; Helicobacter pylori
doi:10.1136/gut.47.5.638
PMCID: PMC1728117  PMID: 11034579
14.  Unexplained fever in neonates may be associated with hepatitis B vaccine 
AIM—To investigate whether hepatitis B vaccination has increased the number of cases of unexplained neonatal fever.
METHOD—The files of all infants born from 1 January 1991 to 31 December 1992, in whom a diagnosis of "injected antibiotic" or "disease of temperature regulation" was recorded, were reviewed. Those who had unexplained fever of 38°C or higher during the first three days of life were divided into two groups: infants who did not receive the hepatitis B vaccine (1991) and infants who did (1992).
RESULTS—In 1992 the incidence of unexplained fever in hepatitis B vaccinated neonates was significantly higher than in the 1991 group of pre-vaccination neonates (35 out of 5819 (0.6%) vs 14 out of 5010 neonates (0.28%) respectively, p=0.013).
CONCLUSIONS—The increase in the number of cases of unexplained neonatal fever seems to be associated with the introduction of routine hepatitis B vaccination on the first day of life. The possibility that an excess number of neonates will undergo unnecessary procedures and treatment to diagnose unexplained fever justifies planning a controlled study to determine whether these preliminary findings point to a significant problem.


PMCID: PMC1721007  PMID: 10525025
15.  Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation 
BMJ : British Medical Journal  2001;322(7282):321-326.
Objective
To examine the benefits and risks of long term anticoagulation (warfarin) compared with antiplatelet treatment (aspirin/indoprofen) in patients with non-rheumatic atrial fibrillation.
Methods
Meta-analysis of randomised controlled trials from Cochrane library, Medline, Embase, Cinhal, and Sigle from 1966 to December 1999. Odds ratios (95% confidence intervals) calculated to estimate treatment effects.
Outcome measures
Fatal and non-fatal cardiovascular events, reductions of which were classified as benefits. Fatal and major non-fatal bleeding events classified as risks.
Results
No trials were found from before 1989. There were five randomised controlled trials published between 1989-99. There were no significant differences in mortality between the two treatment options (fixed effects model: odd ratio 0.74 (95% confidence interval 0.39 to 1.40) for stroke deaths; 0.86 (0.63 to 1.17) for vascular deaths). There was a borderline significant difference in non-fatal stroke in favour of anticoagulation (0.68 (0.46 to 0.99)); and 0.75 (0.50 to 1.13) after exclusion of one trial with weak methodological design. A random effects model showed no significant difference in combined fatal and non-fatal events (odds ratio 0.79 (0.61 to 1.02)). There were more major bleeding events among patients on anticoagulation than on antiplatelet treatment (odds ratio 1.45 (0.93 to 2.27)). One trial was stopped prematurely after a significant difference in favour of anticoagulation was observed. The only trial to show a significant difference in effect (favouring anticoagulation) was methodologically weaker in design than the others.
Conclusions
The heterogeneity between the trials and the limited data result in considerable uncertainty about the value of long term anticoagulation compared with antiplatelet treatment. The risks of bleeding and the higher cost of anticoagulation make it an even less convincing treatment option.
PMCID: PMC26572  PMID: 11159653
16.  A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport® and Botox® in the treatment of cervical dystonia 
OBJECTIVE—This study was designed to establish whether a ratio of three units of Dysport® is equivalent to one unit of Botox® for the treatment of cervical dystonia.
METHODS—Patients with predominantly rotational cervical dystonia, and a minimum of four previous Botox treatments, were randomised to receive either the clinically indicated dose of Botox or three times that dose in Dysport units. Study botulinum toxin was administered in a double blind fashion, to one or more clinically indicated muscles, at one or more sites per muscle. Patients returned for assessment two, four, eight, and 12 weeks after treatment.
RESULTS—A total of 73 patients (Dysport, 38; Botox, 35) were entered. The Dysport group received a mean (SD) dose of 477 (131) (range 240-720) Dysport units, and the Botox group received a mean (SD) dose of 152 (45) (range 70-240) Botox units. The mean (SEM) post-treatment Tsui scores for the Dysport group (4.8 (0.3)) and the Botox group (5.0 (0.3)) were not statistically different (p=0.66). The study had 91% power to detect a clinically significant difference of two points. Both groups showed substantial improvement in Tsui score by week 2 (mean (SD); Dysport, 46 (28)%; Botox, 37 (28)%), with a peak effect at week 4 (mean (SD); Dysport, 49 (29)%; Botox, 44 (28)%). A similar response profile was seen for other assessments of efficacy. The duration of effect, assessed by time to retreatment, was also similar (mean (SD); Dysport, 83.9 (13.6) days; Botox, 80.7 (14.4) days; p=0.85). During the study 22 of 38 (58%) Dysport patients reported 39 adverse events, and 24 of 35 (69%) Botox patients reported 56 adverse events (p=0.35). A global assessment of efficacy and safety considered that 29 of 38 (76%) Dysport patients and 23 of 35 (66%) Botox patients were treatment successes (p=0.32).
CONCLUSION—Patients with predominantly rotational cervical dystonia treated with the clinically indicated dose of Botox or three times that dose in Dysport units show similar improvements and do not have significantly different safety profiles.


PMCID: PMC2169916  PMID: 9436720
17.  Costs and effectiveness of a nurse specialist anticoagulant service. 
Journal of Clinical Pathology  1997;50(10):823-828.
AIMS: To determine the costs and effectiveness of an anticoagulant nurse specialist service compared with a conventional consultant service based on two hospital sites in northwest Hertfordshire. METHODS: Sequential design comparing retrospectively the conduct and outcomes of a consultant service with a nurse specialist service over two six month periods. In each of the six month study periods, all new patients consecutively referred for anticoagulation over a three month period (group A) at the start of each study period and a random selection of patients who had already been attending the anticoagulant service for one year or more (group B) were included in the study. Group A patients wre followed for up to three months and group B patients for six months. The main outcome measures were costs of service provision and effectiveness. Costs included those for the use of the anticoagulant service, those related to general practitioner (GP) visits and hospitalisations, and running costs (staff time, laboratory tests, patient transport). Measures of effectiveness were the mean proportion of time patients spend in the therapeutic range, the number of drugs being taken that could interact adversely and/or inhibit haemostatic function, and patient and GP satisfaction with service provision. RESULTS: In the consultant service, for group A there were more patients aged 66-75 years (p = 0.004) and fewer patients aged more than 76 years (p = 0.001); and for group B, there were fewer patients on anticoagulation for cardiac conditions (p = 0.001), but more on anticoagulation for thromboembolic conditions (p = 0.02) than in the nurse specialist service. The clinic running costs of the nurse specialist service were 4.99 Pounds per attendance, compared with 4.75 Pounds in the consultant service. Including all other costs related to treatment, there was no statistically significant difference in cost per patient. There was no significant difference in the proportion of time patients spent in the therapeutic range between the consultant service and the nurse specialist service. In the nurse specialist service, fewer patients in group A were taking drugs that could interact adversely and/or inhibit haemostatic function (p = 0.01) and more patients were satisfied with service provision (p = 0.04) compared with the consultant service. There was no significant variation in GP satisfaction between the two services. CONCLUSION: In the provision of outpatient anticoagulation, the nurse specialist service was no more expensive than the consultant service and, using our primary outcome, at least as effective. The nurse specialist service has some clear advantages compared to the consultant service: provision of domicilliary care for housebound patients, fewer new patients taking drugs that could interact adversely and/or inhibit haemostatic function patients, it is preferred by newly referred patients to the consultant service, and it is as acceptable to their GPs.
PMCID: PMC500262  PMID: 9462263
18.  Bacteroides fragilis enterotoxin gene sequences in patients with inflammatory bowel disease. 
Emerging Infectious Diseases  2000;6(2):171-174.
We identified enterotoxigenic Bacteroides fragilis in stool specimens of patients with inflammatory bowel disease and other gastrointestinal disorders. The organism was detected in 11 (13.2%) of 83 patients with inflammatory bowel disease. Of 57 patients with active disease, 19.3% were toxin positive; none of those with inactive disease had specimens positive for enterotoxigenic Bacteroides fragilis gene sequences.
PMCID: PMC2640860  PMID: 10756151
19.  Bioterrorism "preparedness": dual use or poor excuse? 
Public Health Reports  2000;115(5):403-406.
Images
PMCID: PMC1308593  PMID: 11236011
20.  Serious hazards of transfusion (SHOT) initiative: analysis of the first two annual reports 
BMJ : British Medical Journal  1999;319(7201):16-19.
Objective
To receive and collate reports of death or major complications of transfusion of blood or components.
Design
Haematologists were invited confidentially to report deaths and major complications after blood transfusion during October 1996 to September 1998.
Setting
Hospitals in United Kingdom and Ireland.
Subjects
Patients who died or experienced serious complications, as defined below, associated with transfusion of red cells, platelets, fresh frozen plasma, or cryoprecipitate.
Main outcome measures
Death, “wrong” blood transfused to patient, acute and delayed transfusion reactions, transfusion related acute lung injury, transfusion associated graft versus host disease, post-transfusion purpura, and infection transmitted by transfusion. Circumstances relating to these cases and relative frequency of complications.
Results
Over 24 months, 366 cases were reported, of which 191 (52%) were “wrong blood to patient” episodes. Analysis of these revealed multiple errors of identification, often beginning when blood was collected from the blood bank. There were 22 deaths from all causes, including three from ABO incompatibility. There were 12 infections: four bacterial (one fatal), seven viral, and one fatal case of malaria. During the second 12 months, 164/424 hospitals (39%) submitted a “nil to report” return.
Conclusions
Transfusion is now extremely safe, but vigilance is needed to ensure correct identification of blood and patient. Staff education should include awareness of ABO incompatibility and bacterial contamination as causes of life threatening reactions to blood.
Key messagesBlood transfusion, while extremely safe, has several potentially fatal hazardsAll staff handling blood should be aware of the importance of correct identity of sample, patient, and blood bag at all stagesResources should be directed to evaluation of methods for improving identification of patientsAcute fever or collapse during or after transfusion may be due to ABO incompatibility or bacterial contaminationMicrobiological complications of transfusion accounted for a minor component of all reports
PMCID: PMC28147  PMID: 10390452
22.  Intervention to reduce telephone prescription requests. 
Canadian Family Physician  1997;43:1952-1956.
OBJECTIVE: To evaluate a systematic effort to reduce telephone orders for prescription medications in a community family practice. DESIGN: Three-year intervention project. SETTING: Solo family practice in Ottawa. PARTICIPANTS: All patients requesting telephone orders for prescription medications. INTERVENTIONS: A retrospective analysis of phone requests and orders was conducted on 1 continuous year's records. A new office policy was instituted on October 9, 1992, discouraging telephone orders for prescription medication. Prescription telephone requests and orders were then monitored continuously for the next 3 years. MAIN OUTCOME MEASURES: Number of telephone prescription requests and orders per half-day 1 year before the intervention compared with the number for the 3 years after the intervention. RESULTS: One year before the intervention, there were 4.96 telephone prescription requests per half-day: 3 years after the intervention this number fell to 0.85. One year before the intervention, the number of telephone prescription orders per half-day was 4.80; this number fell continuously to 0.67 during the 3 years following the intervention. CONCLUSIONS: We observed a reduction in the number of telephone prescription requests and orders following the introduction of an office policy that encouraged prescribing and renewing medication in person.
PMCID: PMC2255211  PMID: 9386882
23.  Helicobacter pylori. 
Clinical Microbiology Reviews  1997;10(4):720-741.
Helicobacter pylori is a gram-negative bacterium which causes chronic gastritis and plays important roles in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. H. pylori has been found in the stomachs of humans in all parts of the world. In developing countries, 70 to 90% of the population carries H. pylori. In developed countries, the prevalence of infection is lower. There appears to be no substantial reservoir of H. pylori aside from the human stomach. Transmission can occur by iatrogenic, fecal-oral, and oral-oral routes. H. pylori is able to colonize and persist in a unique biological niche within the gastric lumen. All fresh isolates of H. pylori express significant urease activity, which appears essential to the survival and pathogenesis of the bacterium. A variety of tests to diagnose H. pylori infection are now available. Histological examination of gastric tissue, culture, rapid urease testing, DNA probes, and PCR analysis, when used to test gastric tissue, all require endoscopy. In contrast, breath tests, serology, gastric juice PCR, and urinary excretion of [15N]ammonia are noninvasive tests that do not require endoscopy. In this review, we highlight advances in the detection of the presence of the organism and methods of differentiating among types of H. pylori, and we provide a background for appropriate chemotherapy of the infection.
PMCID: PMC172942  PMID: 9336670
24.  The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity. 
Molecular and Cellular Biology  1997;17(9):5629-5639.
The von Hippel-Lindau tumor suppressor gene (VHL) has a critical role in the pathogenesis of clear-cell renal cell carcinoma (RCC), as VHL mutations have been found in both von Hippel-Lindau disease-associated and sporadic RCCs. Recent studies suggest that vascular endothelial growth factor (VEGF) mRNA is upregulated in RCC- and von Hippel-Lindau disease-associated tumors. We have therefore assessed the effect of the VHL gene product on VEGF expression. VEGF promoter-luciferase constructs were transiently cotransfected with a wild-type VHL (wt-VHL) vector in several cell lines, including 293 embryonic kidney and RCC cell lines. wt-VHL protein inhibited VEGF promoter activity in a dose-dependent manner up to 5- to 10-fold. Deletion analysis defined a 144-bp region of the VEGF promoter necessary for VHL repression. This VHL-responsive element is GC rich and specifically binds the transcription factor Sp1 in crude nuclear extracts. In Drosophila cells, cotransfected VHL represses Sp1-mediated activation but not basal activity of the VEGF promoter. We next demonstrated in coimmunoprecipitates that VHL and Sp1 were part of the same complex and, by using a glutathione-S-transferase-VHL fusion protein and purified Sp1, that VHL and Sp1 directly interact. Furthermore, endogenous VEGF mRNA levels were suppressed in permanent RCC cell lines expressing wt-VHL, and nuclear run-on studies indicated that VHL regulation of VEGF occurs at least partly at the transcriptional level. These observations support a new mechanism for VHL-mediated transcriptional repression via a direct inhibitory action on Sp1 and suggest that loss of Sp1 inhibition may be important in the pathogenesis of von Hippel-Lindau disease and RCC.
PMCID: PMC232411  PMID: 9271438
25.  Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies) 
BMJ : British Medical Journal  1997;314(7076):253-257.
OBJECTIVE: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies). DESIGN: Randomised controlled trial. SETTING: Specialist clinic for recurrent miscarriages. SUBJECTS: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies. INTERVENTION: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks' gestation. MAIN OUTCOME MEASURES: Rate of live births with the two treatments. RESULTS: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%). CONCLUSION: Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.
PMCID: PMC2125731  PMID: 9022487

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