A model for malaria treatment evaluation in the presence of multiple species.

Plasmodium falciparum and P. vivax are the two most common causes of malaria. While the majority of deaths and severe morbidity are due to P. falciparum, P. vivax poses a greater challenge to eliminating malaria outside of Africa due to its ability to form latent liver stage parasites (hypnozoites), which can cause relapsing episodes within an individual patient. In areas where P. falciparum and P. vivax are co-endemic, individuals can carry parasites of both species simultaneously. These mixed infections complicate dynamics in several ways: treatment of mixed infections will simultaneously affect both species, P. falciparum can mask the detection of P. vivax, and it has been hypothesised that clearing P. falciparum may trigger a relapse of dormant P. vivax. When mixed infections are treated for only blood-stage parasites, patients are at risk of relapse infections due to P. vivax hypnozoites. We present a stochastic mathematical model that captures interactions between P. falciparum and P. vivax, and incorporates both standard schizonticidal treatment (which targets blood-stage parasites) and radical cure treatment (which additionally targets liver-stage parasites). We apply this model via a hypothetical simulation study to assess the implications of different treatment coverages of radical cure for mixed and P. vivax infections and a "unified radical cure" treatment strategy where P. falciparum, P. vivax, and mixed infections all receive radical cure after screening glucose-6-phosphate dehydrogenase (G6PD) normal. In addition, we investigated the impact of mass drug administration (MDA) of blood-stage treatment. We find that a unified radical cure strategy leads to a substantially lower incidence of malaria cases and deaths overall. MDA with schizonticidal treatment was found to decrease P. falciparum with little effect on P. vivax. We perform a univariate sensitivity analysis to highlight important model parameters.

The anatomical footprint of the Achilles tendon: a cadaveric study.

We dissected 12 fresh-frozen leg specimens to identify the insertional footprint of each fascicle of the Achilles tendon on the calcaneum in relation to their corresponding muscles. A further ten embalmed specimens were examined to confirm an observation on the retrocalcaneal bursa. The superficial part of the insertion of the Achilles tendon is represented by fascicles from the medial head of the gastrocnemius muscle, which is inserted over the entire width of the inferior facet of the calcaneal tuberosity. In three specimens this insertion was in continuity with the plantar fascia in the form of periosteum. The deep part of the insertion of the Achilles tendon is made of fascicles from the soleus tendon, which insert on the medial aspect of the middle facet of the calcaneal tuberosity, while the fascicles of the lateral head of the gastrocnemius tendon insert on the lateral aspect of the middle facet of the calcaneal tuberosity. A bicameral retrocalcaneal bursa was present in 15 of the 22 examined specimens. This new observation and description of the insertional footprint of the Achilles tendon and the retrocalcaneal bursa may allow a better understanding of the function of each muscular part of the gastrosoleus complex. This may have clinical relevance in the treatment of Achilles tendinopathies.

Towards a web services infrastructure for perinatal, obstetrical, and neonatal clinical decision support.

This paper presents the design of a unifying infrastructure for clinical decision support systems (CDSSs) and medical data relating to the perinatal life cycle. The diverse CDSSs designed for deployment within the perinatal life cycle to improve care, such as Artificial Neural Networks and Case-Based Reasoners, are integrated using the eXtended Markup Language (XML) and are subsequently offered as a secure web service. These web services are accessible from anywhere within the hospital information system and from remote authorized sites. The goal of such an infrastructure is to provide integrated CDSS processing in a complex distributed environment, in order to support real-time physician decision-making. This design provides a novel web services infrastructure implementation and offers a strong case study for deploying and evaluating the web services paradigm within a health care environment.

Influence of missing values on artificial neural network performance.

The problem of databases containing missing values is a common one in the medical environment. Researchers must find a way to incorporate the incomplete data into the data set to use those cases in their experiments. Artificial neural networks (ANNs) cannot interpret missing values, and when a database is highly skewed, ANNs have difficulty identifying the factors leading to a rare outcome. This study investigates the impact on ANN performance when predicting neonatal mortality of increasing the number of cases with missing values in the data sets. Although previous work using the Canadian Neonatal Intensive Care Unit (NICU) Network s database showed that the ANN could not correctly classify any patients who died when the missing values were replaced with normal or mean values, this problem did not arise as expected in this study. Instead, the ANN consistently performed better than the constant predictor (which classifies all cases as belonging to the outcome with the highest training set a priori probability) with a 0.6-1.3% improvement over the constant predictor. The sensitivity of the models ranged from 14.5-20.3% and the specificity ranged from 99.2- 99.7%. These results indicate that nearly 1 in 5 babies who will eventually die are correctly classified by the ANN, and very few babies were incorrectly identified as patients who will die. These findings are important for patient care, counselling of parents and resource allocation.

Movement of the knee in osteoarthritis. The use of electrogoniometry to assess function.

We used electrogoniometers to measure the range of movement (ROM) of the knee during various activities, comparing 50 patients with osteoarthritis of the knee (OA) with 20 healthy age- and sex-matched subjects. The minimum and maximum joint angles and the ranges of excursion of the patient and control groups were tested for significant differences, using an unrelated Student's t-test with pooled variance. Knee flexion in patients with OA was significantly reduced during all activities (p < 0.05), but differences in knee extension were not significant except when patients negotiated stairs. We believe that this reduction in ROM is caused by inhibition due to pain when load-bearing. Static non-load-bearing measurements of the ROM poorly reflected the functional ROM, with a coefficient of determination (r2) of 0.59 in the patient group and 0.60 in the control group. Electrogoniometry of the ROM of the knee provides a reliable, accurate and objective measurement of knee function.

Escherichia coli alpha-hemolysin (HlyA) is heterogeneously acylated in vivo with 14-, 15-, and 17-carbon fatty acids.

alpha-Hemolysin (HlyA) is a secreted protein virulence factor observed in certain uropathogenic strains of Escherichia coli. The active, mature form of HlyA is produced by posttranslational modification of the protoxin that is mediated by acyl carrier protein and an acyltransferase, HlyC. We have now shown using mass spectrometry that these modifications, when observed in protein isolated in vivo, consist of acylation at the epsilon-amino groups of two internal lysine residues, at positions 564 and 690, with saturated 14- (68%), 15- (26%), and 17- (6%) carbon amide-linked side chains. Thus, HlyA activated in vivo consists of a heterogeneous family of up to nine different covalent structures, and the substrate specificity of the HlyC acyltransferase appears to differ from that of the closely related CyaC acyltransferase expressed by Bordetella pertussis.

Discharge of mothers and babies from hospital after birth of a healthy full-term infant: developing criteria through a community-wide consensus process.

OBJECTIVE: To ensure safe care of mothers and babies after birth, irrespective of length of hospital stay, and to ensure effective links between hospital and community postnatal services. METHODS: Program aimed toward consumers and professionals working with them in Ottawa-Carleton (750,000 persons.) All pregnant women in the community included. Program developed by professionals, institutions and community agencies. Information on current practices elsewhere and early discharge literature studied. New provincial survey on practice changes performed in Ontario. Emergency room utilization data analyzed. Discharge and post-discharge criteria, and a common prenatal education curriculum, developed. RESULTS: Multidisciplinary, multi-sectoral committees, institutions and agencies have developed programs for appropriate discharge practice and improved postnatal follow-up. Professionals have supported flexible discharge guidelines. CONCLUSIONS: Provided discharge criteria and follow-up are available, flexible discharge timing and safety appear compatible. The Ottawa-Carleton process to develop criteria and programs has allowed a collaborative, consensus-based approach to 'early' newborn discharge.

Intraoperative bacterial contamination in operations for joint replacement.

All surgical operations have the potential for contamination, and the equipment used can harbour bacteria. We collected samples from 100 elective primary hip and knee arthroplasties. These showed rates of contamination of 11.4% for the sucker tips, 14.5% for light handles, 9.4% for skin blades and 3.2% for the inside blades used during surgery; 28.7% of gloves used for preparation were also contaminated. Of the samples taken from the collection bags used during hip arthroplasty, 20% grew bacteria, which represents a significant microbial reservoir. Also, 17% of theatre gowns were contaminated at the end of the operation. Contamination was found in 10% of the needles used during closure of the fascia. Overall, 76% of the organisms grown were coagulase-negative staphylococcus. A total of 63% of operations showed contamination in the field of operation. Some changes in practice are suggested. Follow-up for a minimum of two years revealed one deep infection but the organism was not identified as a contaminant. These data provide a baseline for studying the bacteriology of the surgery of revision arthroplasty.

Extension of the elbow and supracondylar fractures in children.

We tested the hypothesis that children who sustain a supracondylar fracture have a greater range of elbow hyperextension than those with a fracture of the distal radius. Three observers made 358 measurements in 183 children (114 boys and 69 girls). There were 119 fractures of the distal radius and 64 supracondylar fractures. Initially, the group with a supracondylar fracture appeared to have extension 1.7 degrees greater than that of the group with fracture of the distal radius. On average, there was a maximum variation of 3 degrees between observers. After allowing for age, gender and observer, there was no significant difference between the groups. Our study had greater than 80% power to detect a difference in hyperextension of 2 degrees at the 5% level with the above observer variability. When age and gender are taken into account, any variation in the amount of hyperextension at the elbow is not sufficient to explain the occurrence of a supracondylar fracture.

Care of the umbilical cord after birth: A limited review of recent literature.

A 1992 meta-analysis did not find enough evidence to recommend one method of umbilical cord care as the 'best'. However, certain agents were deemed acceptable including triple dye, silver sulfadiazine and antibiotic ointments. In this paper, the authors sought to discover whether there was now evidence to support one specific method of cord care over others for the prevention of bacterial infection. After a limited search of the English language literature published in the past 10 years, little evidence was found to suggest that treatments to sterilize or speed up the drying of the umbilical cord were either routinely necessary or efficacious. Results from nine studies are summarized in this paper.

Specific recognition of thymic self-peptides induces the positive selection of cytotoxic T lymphocytes.

To understand how thymic selection gives rise to T cells that are capable of major histocompatibility complex (MHC)-restricted recognition of antigen but are tolerant of self, we directly examined how peptide/MHC ligands expressed on thymic epithelial cells trigger the positive selection of immature thymocytes. We demonstrate that abundant self-peptides, purified from the H-2D(b) molecules of thymic epithelial cells, are specifically recognized during the positive selection of CD8+ T cells, implying that positive selection generates a repertoire of T cells that is weakly self-reactive. We also found that this recognition is somewhat cross-reactive, thereby providing an explanation for how the specific recognition of a limited repertoire of thymic self-peptides can select a diverse repertoire of T cells.

Interleukin-6 expression in cord blood of patients with clinical chorioamnionitis.

The objective of this study was to define whether IL-6 is an early marker of infection in the newborn. To correlate the occurrence of clinical chorioamnionitis with the levels of IL-6 expression in neonates, IL-6 was measured in cord plasma by ELISA and in mononuclear cells by reverse transcriptase-PCR before and after mitogenic stimulation. Eight neonates were included in each of the following four groups: elective cesarean section, uncomplicated normal spontaneous vaginal delivery, delivery after prolonged rupture of amniotic membranes with no evidence of chorioamnionitis, and delivery with evidence of chorioamnionitis. All 32 neonates were clinically well after delivery, and all 16 babies with prolonged rupture of membranes or clinical chorioamnionitis had negative blood cultures. Elevated IL-6 levels were found only in neonates born to mothers with chorioamnionitis (119.7 +/- 33.5 pg/mL versus 2.71 +/- 0.59 pg/mL, p < 0.005). Mononuclear cells from five of these neonates expressed no IL-6 mRNA in vivo despite elevated levels of IL-6 in their cord plasma. Cord blood mononuclear cells from healthy term babies were capable of synthesizing IL-6 in vitro in response to stimulation with bacterial lipopolysaccharide. These results suggest that IL-6 levels in cord plasma increased with clinical chorioamnionitis, despite the lack of evidence of infection in the neonates. Therefore, we conclude that, although a high level of IL-6 may be a good marker of chorioamnionitis, it may not be a specific marker of infection in the newborn.

Case report: complete photopenia of the femoral head on radionuclide bone scanning in septic arthritis of the hip.

Three cases of septic arthritis of the hip are presented. In each case, radionuclide bone scanning, using 99Tcm diphosphonate (MDP), demonstrated complete photopenia of the femoral head. All three cases resulted in avascular necrosis and subsequently had a poor clinical outcome with a reduced range of movement and radiographic epiphyseal deformity. Complete photopenia in the presence of suspected sepsis requires urgent referral with a view to exploration and decompression.

Lower limb amputation following injury: a survey of long-term functional outcome.

Although there have been significant advances in surgical methods of limb preservation and various injury scores produced to predict the outcome after severe lower limb injury, there is common belief amongst surgeons that patients rehabilitate rapidly and well after amputation. There is however little evidence in the literature supporting this view of functional outcome of amputation following injury. A subjective assessment of post-injury lower limb amputees implied that there was a similar functional outcome in above- and below-knee amputations. Furthermore, there was little functional difference between early and delayed amputations, the delayed group being more satisfied with the end result.

Five to eight year results of the Johnson-Elloy (Accord) total knee arthroplasty.

Between February 1982 and December 1985, 133 knees in 107 patients were replaced with a cemented Johnson-Elloy (Accord) total knee arthroplasty. Thirty-five knees were lost during the follow-up period because of death in 29, revision in 3, infection in 1, and refusal of follow-up evaluation in 2. The results of the remaining 98 knees in 76 patients with a 5-8 year follow-up period are presented. The procedure was carried out in all cases presenting for surgery, irrespective of pathology and degree of deformity. The range of flexion achieved as a mean of 93.5 degrees in the osteoarthritic group and 100 degrees in the rheumatoid arthritic group. Eighty-seven percent of the osteoarthritic group and 95% of the rheumatoid arthritic group achieved between 10 degrees and 50 degrees of rotation at 90 degrees of flexion, which was maintained for the duration of the study. Adequate stability in both groups, valgus-varus and rotation in extension, and anteroposterior in flexion was achieved. Survivorship was 97.7% at 80 months.

Dexamethasone therapy for bronchopulmonary dysplasia: improved respiratory mechanics without adrenal suppression.

The purpose of the present study was to examine the pattern of changes in respiratory system mechanics induced by dexamethasone (Dex) in infants with bronchopulmonary dysplasia (BPD) and to determine whether dosages that produce these changes induce adrenal suppression. We examined mechanics in seven ventilator-dependent premature infants (age, 33 +/- 4.8 days) with BPD, before and daily during Dex therapy. Dex (0.5 mg/kg/day) was given intravenously for 7 days unless complications necessitated early termination. Respiratory system resistance (Rrs) and compliance (Crs) were measured by the passive expiratory flow-volume technique during the course of dexamethasone therapy or until extubation. Adrenocorticotrophic hormone (ACTH) stimulation tests were done at baseline and following Dex therapy to evaluate adrenal function. Dex therapy caused a 77 +/- 18% increase in Crs (from 0.97 +/- 0.09 SEM mL/cmH2O to 1.6 +/- 0.16 mL/cmH2O; P less than 0.025) and a 33 +/- 5% decrease in Rrs (from 0.20 +/- 0.02 cmH2O/mL/s to 0.14 +/- 0.01 cmH2O/mL/s; P less than 0.01). Concurrently, ventilator rate, mean airway pressure, and FIO2 all decreased significantly (P less than 0.025). Extubation occurred later in infants with the lowest Crs and highest Rrs at baseline. At extubation, all Crs values were greater than 1.33 mL/cmH2O and Rrs values were less than 0.15 cmH2O/mL/s. Systolic blood pressure increased from 61 +/- 6.3 mmHg to 84 +/- 17 mmHg, 72-96 h after the start of Dex (P less than 0.025). There were no episodes of culture-positive sepsis. Neither basal nor ACTH-stimulated levels of cortisol were suppressed as a result of Dex therapy (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Colon cancer in blacks: a disease with a worsening prognosis.

Despite the fact that a significant national effort has been made over the past 10 years to improve the early detection and treatment of colorectal cancer, blacks have not had any change in their prognosis compared to whites, and their survival rate appears to be independent of stage at the time of diagnosis. The disease incidence is practically the same for both races, 49 per 100,000. We reviewed all patients with colorectal cancer in our Tumor Registry over a 10-year period to determine whether the experience at an all-black institution with a black patient base for much of its history would help clarify these crucial questions. There were 118 cases (73 women/45 men), and the mean age was 68 years (range: 29 to 93). The most common signs and symptoms were gross bleeding (34%) and abdominal pain (30%), with most patients presenting with a combination of symptoms. Remarkably, none were symptom-free. Of the 96 patients who were staged surgically and pathologically, 68 (71%) were beyond Duke's B staging at the time of diagnosis and surgery. The overall 5-year survival rate was 47%, significantly related to stage of disease at diagnosis (P less than .001). We concluded that blacks have not shared in the progress made in early diagnosis and treatment of colon cancer, and that special attention should be given to developing screening and surveillance methodology targeted specifically at blacks.