Removal of infected cemented hinge knee prostheses using extended femoral and tibial osteotomies: six cases.

Extended femoral and tibial osteotomies were performed to remove infected cemented hinged knee prostheses in five patients (six knees) with a mean age of 72 years (44-85) and a history of multiple knee surgeries. A tibial osteotomy was used to mobilise the distal quadriceps insertion and to release the tibial extension. The femoral component was extracted by downward traction and its cement mantle was cleared through an anterior osteotomy (n=4) or via the distal approach (n=2). The bone flaps were re-approximated by wire cerclage over articulating acrylic spacers. Mean time to re-implantation of a new knee prosthesis was 11 months (6-24). Revision prostheses with cement fixation restricted to the epiphyseal-metaphyseal region were used. Infection recurred in two cases at 16 and 4 months after the prosthetic re-implantation, and was managed by joint fusion for one and irrigation/lavage for the other, respectively. At last follow-up after a mean of 53 months, the mean Parker score was 4 ± 2, the mean IKS knee score was 66 ± 25 (28-93), and the mean IKS function score was 7 ± 16 (0-40). This technique facilitates the removal of infected cemented components of hinge prostheses and of the cement mantle, most notably in the absence of loosening, without compromising re-implantation of a new knee prosthesis.

Surgical management of pelvic primary bone tumors involving the sacroiliac joint.

INTRODUCTION: Pelvic primary malignant bone tumours, especially when involving the sacroiliac joint are difficult to treat. Abdominoperineal amputations are today used, only in life-threatening situations. HYPOTHESIS: A precisely planed surgical technique can save the affected extremity without compromising the resection quality and subsequent patient survival. OBJECTIVE: To assess the procedures used for resection and reconstruction of bone tumours invading the sacroiliac joint as well as their effects on cancer outcome and functional results. MATERIALS AND METHODS: This is a continuous and retrospective analysis of 24 patients treated between 1986 and 2003. Six tumours affected the sacral body and 18 tumours involved the wing of the ilium. The joint articular surface was invaded in only six cases. Seventeen patients received neoadjuvant chemotherapy. The procedure was performed through an enlarged iliac crest incision, giving access to two sections of the pelvic ring. Six cases required neurological sacrifice. Initial tumour grading was based on the Enneking classification, and the functional results, on the Musculoskeletal Tumour Society (MSTS) scoring system. RESULTS: The average operation lasted 5.27 hours. Reconstruction was performed with bone autograft and instrumentation. Resection was large with adequate margins 11 times, marginal 12 times, and contaminated once. Average follow-up was 4.77 years. The 5-year survival rate was 50%. Twelve patients either died from their disease or were in the metastatic stage at final follow-up. Survival was linked to the quality of resection and initial tumour staging. Hemisacrectomy did not affect patient survival. Local recurrences had a poor prognosis with eight cases of secondary metastases out of 11. Bone healing occurred in 13 patients, 10 of whom survived. Of the 12 patients who survived and were in complete remission at final follow-up, the average MSTS score was 61%. The score was at 38.6% in cases involving neurological sacrifice, and at 77.1% for the rest of the group. It was at 64% in healed cases and 13% in nonunion cases. DISCUSSION: The survival of patients presenting with a sacroiliac joint tumour is substantially related to both tumour histology and resection quality. Local recurrences carry a poor prognosis with a high rate of secondary metastatic dissemination. In situations where disease control can be achieved, the proposed method of reconstruction allows, satisfactory bone healing and fair functional recovery, provided no major neurological sacrifice has taken place. LEVEL OF EVIDENCE: level IV: Retrospective Therapeutic Study.

Closed reduction with traction for developmental dysplasia of the hip in children aged between one and five years.

The treatment of developmental dysplasia of the hip diagnosed after the first year of life remains controversial. A series of 36 children (47 hips), aged between one and 4.9 years underwent gradual closed reduction using the Petit-Morel method. A pelvic osteotomy was required in 43 hips (91.5%). The patients whose hips did not require pelvic osteotomy were among the youngest. The mean age at final follow-up was 16.1 years (11.3 to 32). The mean follow-up was 14.3 years (10 to 30). At the latest follow-up, 44 hips (93.6%) were graded as excellent or good according to the Severin classification. Closed reduction failed in only two hips (4.3%) which then required open reduction. Mild avascular necrosis was observed in one (2.1%). The accuracy of the reduction and associated low complication rate justify the use of the Petit-Morel technique as the treatment of choice for developmental dysplasia of the hip in patients aged between one and five years.

Introducing printed postpartum orders for measles-mumps-rubella vaccination: a qualitative study.

OBJECTIVE: After introducing printed postpartum orders at our centre, we observed a large increase in measles-mumps-rubella (MMR) vaccination of susceptible women. The objective of this study was to ascertain factors responsible for the success of our approach and to identify potential obstacles so as to facilitate the implementation of similar policies at other hospitals. METHODS: For this qualitative study, taped semi-structured interviews were carried out with physicians, nurses, and a ward clerk regarding their views on postpartum MMR vaccination and on various aspects of implementing a printed postpartum order sheet that included MMR vaccination of susceptible women. Interviews were transcribed and the responses classified by theme. Thematic analysis was used to identify strengths and weaknesses of this approach. RESULTS: Following implementation of printed postpartum orders that included MMR vaccination of susceptible women, the proportion of eligible women vaccinated increased from 12.1 to 81.7% (risk ratio 6.8, 95% confidence interval [CI] 3.3, 13.7). While the physician and nursing staff broadly supported this initiative, we identified the need for changes in obstetrical care and documentation: most importantly, a comprehensive protocol with supporting information and guidelines should be provided for postpartum nurses; and a system must be in place to ensure that the completed antenatal record, including screening test results, be available in the expected hospital of delivery by the late second trimester. CONCLUSION: Previously undocumented claims that standing orders for postpartum MMR vaccination will increase the rate of vaccination of susceptible women have now been substantiated at one centre. Nevertheless, careful infrastructure and systems changes are required to ensure implementation of such orders.

First Report of Pepino mosaic virus in Canada and the United States.

During the winter of 2000, tomatoes (Lycopersicon esculentum) with a bright yellow leaf mosaic were observed in a commercial greenhouse in southern Ontario, Canada. Examination of leaf extracts, using leaf dips and immunosorbent absorption electron microscopy (ISEM), showed flexuous rods consistent with the potexvirus group. Polyclonal antibodies raised against the original Peruvian Pepino mosaic virus (PepMV) isolate (1) and commercial antibodies obtained from Deutsche Sammlung von Mikro-organismen und Zellkulturen (DSMZ), GmbH, Braunsweig, Germany, and Plant Research International (PRI), Wageningen, the Netherlands, were used in ISEM. Leaves tested positive in double-antibody sandwich-enzyme-linked immunosorbent assay (ELISA) with antibodies from DSMZ and PRI. A triple-antibody sandwich-ELISA obtained from Adgen Ltd. (Nellies Gate, UK) gave similar results. Potato virus X did not react with PepMV antiserum in ELISA. Positive PepMV ELISA controls were a U.K. and a Dutch isolate supplied by R. Mumford and R. A. A. van Vlugt, respectively, and DSMZ. Using primers generated from a sequence of the RNA polymerase region of a U.K. PepMV isolate (R. Mumford, unpublished data), a reverse transcription-polymerase chain reaction test showed the expected 312-bp amplicon for the Canadian, Dutch, and U.K. isolates. The primer sequences used were forward 5' CTA TTA CAA CTC CGG AAG CCA 3' and reverse 5' TGG TCT GGC CAG GCT TTG AC 3'. The three isolates were maintained in tomato cv. Bush Beefsteak. When mechanically inoculated on L. esculentum cv. Rapsodie, the Canadian isolate caused a bright yellow mosaic in 1 to 2 weeks, while the two European isolates caused a faint yellow mosaic and mild puckering of the leaves. When mechanically inoculated on 17 indicator plants, the Canadian isolate had a host range similar to the U.K. isolate. The most striking difference in symptoms occurred in L. pimpinellifolium, in which the Canadian isolate caused a yellow mosaic, the Dutch isolate caused no symptoms, and the U.K. isolate caused a marked puckering of the leaves, suggesting virus strain differences among the isolates. Tomato fruits originating from the United States were collected during border inspections by the Canadian Food Inspection Agency and tested for PepMV by ELISA with antisera from DSMZ. PepMV was not detected in 7 samples from California, but was detected in 6 of 12 samples from Colorado, 6 of 7 samples from Arizona, and 1 of 5 samples from Texas. PepMV was originally isolated from pepino (Solanum muricatum) in Peru in 1980 (1) and subsequently from tomato in the Netherlands in 1999 (2). To our knowledge, this is the first report of PepMV in North America. References: (1) R. Jones et al. Ann. Appl. Biol. 94:61, 1980. (2) R. A. A. van Vlugt et al. Plant Dis. 84:103, 2000.

Characterization of hch, the Podospora anserina homolog of the het-c heterokaryon incompatibility gene of Neurospora crassa.

The het-c locus controls heterokaryon formation in Neurospora crassa. It is subject to balancing selection operating to maintain polymorphism at that locus in natural populations. We have isolated hch, the het-c homolog from the related species Podospora anserina (hch for het-c homolog), in order to determine if this gene also functions as a het gene in that species. The het-c and hch sequences are highly similar but differ in the region defining allele specificity in N. crassa het-c. Analysis of hch variability in 11 natural P. anserina isolates with different het genotypes revealed no polymorphism. This suggested that hch does not function as a het gene. However, heterologous expression of the N. crassa het-cPA allele in P. anserina triggers a growth defect reminiscent of the het-c incompatibility reaction.

Sensitivity of human type II topoisomerases to DNA damage: stimulation of enzyme-mediated DNA cleavage by abasic, oxidized and alkylated lesions.

Type II topoisomerases are essential enzymes that are also the primary cellular targets for a number of important anticancer drugs. These drugs act by increasing levels of topoisomerase II-mediated DNA cleavage. Recent studies indicate that endogenous forms of DNA damage, such as abasic sites and base mismatches, also stimulate the DNA scission activity of the enzyme. To extend our understanding of how type II topoisomerases react to DNA damage, the effects of abasic sites, and oxidized and alkylated bases on DNA cleavage mediated by human topo-isomerase IIalpha and beta were determined. Based on experiments that incorporated random abasic sites into plasmid DNA, human type II enzymes can locate lesions even within a background of several thousand undamaged base pairs. As determined by experiments that utilized site-specific forms of DNA lesions, oxidized or monoalkylated purines that allow base pairing and induce little distortion in the double helix have modest effects on topoisomerase II-mediated DNA cleavage. In contrast, 1,N(6)-ethenoadenine, a bulky lesion that disrupts base pairing, enhanced DNA cleavage approximately 10-fold. 1,N(6)-Ethenoadenine is the first lesion found to rival the stimulatory effects of apurinic sites on the DNA scission activity of eukaryotic type II topoisomerases.

[The evolution of ethical standards in the practice of psychology: a reflection on the APA Code of Ethics].

After briefly describing the need for ethics in the development of professional regulation and analyzing the historical emergence of codes of ethics, the goal of this paper is to scrutinize the process by which the American Psychological Association developed its own Code of Ethics and proceeded to revise it periodically. Different lessons can be derived from these efforts and from the criticisms that were formulated. The need for international standards in professional and research ethics is then considered, and the results of a recent study on this subject are presented. Five major conclusions can be derived from the preceding analysis: (1) Codes of ethics can help professional recognition by stressing the importance given to the protection of the public, (2) the development of a code of ethics is usually related to the advancement of professional practice, (3) ethical standards should be in tune with the cultural values and the belief system of a given community, (4) a well-balanced code should incorporate both general aspirational principles and enforceable standards, and (5) the method used to define principles and standards should be empirically based.

A mutant yeast topoisomerase II (top2G437S) with differential sensitivity to anticancer drugs in the presence and absence of ATP.

To further characterize the mechanistic basis for cellular resistance/hypersensitivity to anticancer drugs, a yeast genetic system was used to select a mutant type II topoisomerase that conferred cellular resistance to CP-115,953, amsacrine, etoposide, and ellipticine. The mutant enzyme contained a single point mutation that converted Gly437 --> Ser (top2G437S). Purified top2G437S displayed wild-type enzymatic activity in the absence of drugs but exhibited two properties that were not predicted by the cellular resistance phenotype. First, in the absence of ATP, it was hypersensitive to all of the drugs examined and hypersensitivity correlated with increased drug affinity. Second, in the presence of ATP, top2G437S lost its hypersensitivity and displayed wild-type drug sensitivity. Since the resistance of yeast harboring top2G437S could not be explained by alterations in enzyme-drug interactions, physiological levels of topoisomerase II were determined. The Gly437 --> Ser mutation reduced the stability of topoisomerase II and decreased the cellular concentration of the enzyme. These findings suggest that the physiological drug resistance phenotype conferred by top2G437S results primarily from its decreased stability. This study highlights the need to analyze both the biochemistry and the physiology of topoisomerase II mutants with altered drug sensitivity in order to define the mechanistic bridge that links enzyme function to cellular phenotype.

Surgical plating of a fractured radius and ulna in a wild Canada lynx.

A free-ranging, adult male Canada-lynx (Lynx canadensis) experienced a closed, complete, non-comminuted transverse fracture of the left radius and ulna when captured in a leg snare. A dynamic compression plate (DCP) attached to the anterior surface of the radius was used to stabilize the fracture. Radiographs 44 days post-surgery indicated advanced primary bone healing. The lynx was released 46 days post-surgery near the site of capture. Radiotelemetry indicated long-term survival and movements similar to other males monitored during the same period.

Oxidative metabolism of 1-(2-chloroethyl)-3-alkyl-3- (methylcarbamoyl)triazenes: formation of chloroacetaldehyde and relevance to biological activity.

(Methylcarbamoyl)triazenes have been shown to be effective cancer chemotherapeutic agents in a number of biological systems. Because of their chemical stability, it is likely that their activity in vivo is the result of a metabolic activation process. Previous studies have shown that 1-(2-chloroethyl)-3-methyl-3-(methylcarbamoyl)triazene (CMM) and 1-(2-chloroethyl)-3-benzyl-3-(methylcarbamoyl)triazene (CBzM) are metabolized by rat liver microsomes in the presence of NADPH to yield the ((hydroxymethyl)carbamoyl)triazene analogs of the parent compounds. The present studies show that both compounds are also oxidized at the chloroethyl substituent to yield chloroacetaldehyde and a substituted urea. In the case of CBzM metabolism, 47% of the metabolized parent compound was recovered as benzylmethylurea, 8% was recovered as benzylurea, and 26% was recovered as the ((hydroxymethyl)carbamoyl)-triazene and carbamoyltriazene metabolites. These results suggest that the chloroethyl group is the favored initial site of metabolism. In reaction mixtures containing initial concentrations of 300 microM CBzM, 78 microM chloroacetaldehyde was produced, as compared to 58 microM chloroacetaldehyde produced from the metabolism of 300 microM CMM. The formation of chloroacetaldehyde, a known mutagenic DNA alkylating agent, may explain the biological activity of these compounds.

The influence of cryogenic brain injury on the pharmacodynamics of pentobarbital. Evidence for a serotonergic mechanism.

To study of the influence of brain injury on the pharmacodynamics of pentobarbital, the authors examined the effect of a focal cortical freezing lesion in rats on the brain concentration of pentobarbital associated with lack of response to tail clamp. The freezing lesion was made with a probe (-50 degrees C) applied through a craniotomy to the intact dura over the left parietal cortex. Three days after injury the rats were anesthetized with a continuous intravenous infusion of pentobarbital until they first did not respond to tail clamp stimulation. The brains were then removed for determination of pentobarbital by high-performance liquid chromatography. The brain pentobarbital concentration required to prevent response to tail clamp (EC50) was reduced from 209 +/- 39 nmol/g (mean +/- standard deviation) in rats without brain injury to 149 +/- 28 nmol/g in the injured animals (P = 0.005). The cortical serotonin (5-HT) concentration was increased from 1904 +/- 358 pmol/g in uninjured rats to 2513 +/- 598 pmol/g (P less than 0.01) in injured animals ipsilateral to the lesion. Pretreatment of the rats with p-chlorophenylalanine (PCPA, 200 mg/kg by intraperitoneal injection) to inhibit 5-HT synthesis abolished both the increase in 5-HT concentration associated with the injury (left cortex, 708 +/- 389 pmol/g; right cortex, 911 +/- 979 pmol/g) and the effect of the lesion on EC50 (uninjured, EC50 = 186 +/- 24 nmol/g; injured, EC50 = 179 +/- 47 nmol/g). Prevention of the decrease in EC50 by inhibition of 5-HT synthesis provides support for a functional role for 5-HT in the influence of cold injury on the pharmacodynamics of pentobarbital.

EEG correlates of hypnotic susceptibility and hypnotic trance: spectral analysis and coherence.

EEG was recorded monopolarly at frontal (F3, F4), central (C3, C4) and occipital (O1, O2) derivations during A-B-A conditions of waking rest, hypnosis (rest, arm immobilization, mosquito hallucination, hypnotic dream), and waking rest. Stringently screened on several measures of hypnotic susceptibility, 12 very low hypnotizable and 12 very highly hypnotizable, right-handed undergraduate, subjects participated in one session. Evaluations were Fast-Fourier spectral analysis, EEG coherence between selected derivations and maximum spectral power within EEG bands. In eyes open and closed conditions in waking and hypnosis, highly hypnotizable subjects generated substantially more mean theta power than did low hypnotizable subjects at all occipital, central and frontal locations in almost all conditions of waking and hypnosis, with a larger difference in frontal locations. Both low and high hypnotizables showed increased mean theta power in hypnosis, suggesting an intensification of attentional processes and imagery enhancement. Mean alpha power was never a predictor of hypnotic susceptibility. Interactions with hypnotic susceptibility showed that highly susceptible subjects had more beta activity in the left than right hemispheres, while low susceptible subjects showed only weak asymmetry. No main effects for or interactions between waking/hypnosis and hypnotic level were found for coherence between derivations or maximum spectral power within theta, alpha and beta EEG bands.

Analgesia and serum concentrations of extradural, subdural and intraperitoneal fentanyl in a rat model.

The effects of epidural, subdural and intraperitoneal fentanyl were determined on the tail flick response of the rat using the response latency as a measure of analgesia. Dose-time-response curves were generated for incremental doses of fentanyl administered at constant injection volumes. Serum concentrations at varying doses were determined using a radioimmunoassay technique. It was found that serum concentrations for extradural, subdural and intraperitoneal fentanyl were similar at the low doses, but differed significantly at higher doses suggesting that pharmacokinetic differences may be concentration dependent. Extradural administration of naloxone (0.004 mg) was able to antagonize extradural fentanyl (8.0 micrograms), a dose eight-fold greater than the lowest maximally effective dose. The relationship between serum fentanyl concentrations and administered doses suggest that the analgesic properties of extradural and subdural fentanyl are in part dependent on centrally mediated actions.

Pharmacokinetics of sufentanil in patients undergoing abdominal aortic surgery.

The authors determined the pharmacokinetics of sufentanil, 12.5 micrograms.kg-1 iv in patients undergoing elective abdominal aortic surgery. The mean age (+/- SD) of the ten patients was 68.4 +/- 7.9 yr; their mean weight was 74.4 +/- 19.1 kg. Six patients underwent aortobifemoral grafting and four had abdominal aortic aneurysm repair. Serum sufentanil concentrations were determined in samples drawn at increasing intervals over a 24-h period. A three-compartment pharmacokinetic model was fit to the concentration versus time data. Total drug clearance was 15.0 +/- 3.2 ml.min-1.kg-1. The volume of distribution at steady-state (Vdss) was 8.7 +/- 4.5 l.kg-1. The elimination half-time were positively correlated with patient age. There were no significant correlations between the pharmacokinetic variables and the duration of aortic cross-clamping, the duration of surgery, or the rate or total volume of iv fluids given intraoperatively. In general surgical patients, the mean elimination half-time of sufentanil has been reported to be 2.7 h. When sufentanil is used in large doses as the primary anesthetic agent for patients undergoing abdominal aortic surgery, the long elimination half-time observed implies that recovery will take much longer than would have been anticipated from previously published pharmacokinetic data.

The pharmacokinetics of alfentanil in children.

The pharmacokinetics of alfentanil were studied in 18 children (3 months to 14 yr of age) undergoing surgery. Alfentanil was administered as a 30-s infusion of either 50 or 120 micrograms.kg-1. Pharmacokinetic values were independent of dose. There was no correlation between Vdss (Volume of distribution at a steady state, measured as l.kg-1) and age or weight, and there was a weak correlation between clearance and age (r = 0.51, P less than 0.05). Vdss and elimination t1/2 were not different in infants less than 1 yr of age when compared to older children. The mean value of Vdss was 0.419 (SE .028) l.kg-1) for the whole group, and elimination t1/2 was 76.3 (SE 6.5) min. The clearance rate [TBC = 7.9 (SE 0.41) ml.kg-1.min-1] was within the range of values previously determined in adult studies. From these data, it would appear that, although there may be differences in the disposition kinetics between children aged 3 months to 14 yr and those measured in adults in some studies by other investigators, age-related differences within this group were not demonstrable.

Modern infusion pumps: are they accurate?

This study examined the volumetric accuracy of six infusion pumps currently available in Canada. Volumes delivered by all pumps over a range of 20-200 ml an hour were within five per cent of their indicated values. The pumps proved to be consistent and unaffected by the height of the infusion bag above the pump or by differing cannulae sizes. A discussion of some of the infusion methods for obtaining clinical accuracy is included.

Measurement of plasma fentanyl concentration: comparison of three methods.

The measurement of plasma fentanyl concentration by radioimmunoassay (RIA) and gas liquid chromatography (GLC) using either a flame ionization detector (FID) or nitrogen/phosphorus detector (NPD) has been compared. RIA is a satisfactory but expensive method of measuring plasma fentanyl concentration. GLC using an FID is not as satisfactory as RIA, but when an NPD is used the results are equal to those of RIA. In addition, other analgesics which are chemically similar to fentanyl, such as alfentanil, may also be measured by the GLC/NPD combination using the same set of operating conditions. By contrast, an RIA method is usually specific for only one compound, and measurement of additional drugs would almost certainly necessitate the development of new assay kits for each one.