Are pain and function better measures of outcome than revision rates after TKR in the younger patient?

Revision is the gold standard outcome measurement for survival analyses of orthopaedic implants but reliance on revision as an endpoint has been recently questioned. This study, that assesses long-term outcome in a specific group of patients who had undergone total knee replacement (TKR) for osteoarthritis, highlights the main problems facing modern survival analyses. Minimum 12-year survival and outcome data were reviewed for a series of sixty patients under the age of 60 years (mean age 55.4 years) who underwent total knee replacement (TKR) for osteoarthritis. The patients are a subgroup from a larger consecutive series of 1429 patients who underwent TKR between 1987 and 1993 at a single institution. Whilst the main study aim was to compare outcome of TKR using different endpoints, the outcome of TKR in this younger subpopulation could also be investigated.With revision as the primary endpoint the survival for TKR was 82.2% (95% CI 17.3). The mean OKS at follow-up (mean 15.7 years) was 30.9. However, many of the 82% of patients who did not undergo revision had a less than satisfactory outcome. 41% of these patients reported modest or severe pain (using the OKS) at final follow-up. A combined endpoint including revision, poor function and significant pain drastically reduced the survival rate for the operation. Survival based on revision alone provides an acceptable but inaccurate impression of outcome in younger TKR patients (under 60 years). A true representation of the success of TKR should include pain and function as endpoints.     

Serum levels of insulin-like growth factor-I and insulin-like growth factor-I binding protein-3: quality control for studies of stored serum.

The insulin-like growth factor (IGF) axis, particularly IGF-I and IGF binding protein-3 (IGFBP-3), has been the subject of much attention because of its role in juvenile growth and their association with cancers at several sites. However, epidemiologic studies of IGF-I and IGFBP-3 have had mixed results and several authors have speculated that quality control (QC), sample storage history, and other methodologic concerns could play a role in this heterogeneity. This article documents the results of storage history and QC efforts for a study of IGF-I and IGFBP-3 in 6,226 serum samples from the National Health and Nutrition Examination Survey III (NHANES III). The study was carried out on site at Diagnostic Systems Laboratories in Webster, Texas, using the IGF-I ELISA (DSL 10-5600) and the IGFBP-3 immunoradiometric assay (DSL 6600). A run-in study of assay performance suggested that plates, days, and weeks significantly affected the variance of both assays. Analysis of samples with different storage histories also indicated strong effects of storage history. Serum samples disbursed to laboratories for measurement of diverse analytes and then returned for storage showed reductions in serum IGF-I level averaging 43% and reductions in IGFBP-3 of 25% compared with samples shipped immediately to the repository for long-term storage at -80 degrees C. Therefore, the main study was carried out using samples that had been shipped directly to the National Center for Health Statistics/NHANES collection center for storage. Laboratory analyses of NHANES III and QC samples were carried out over approximately 10 months. QC was monitored through repeated testing of blood samples from six individuals, with two individuals tested twice on each plate. Assay performance was stable over the entire study and coefficients of variation averaged 2% to 3% within plates and approximately 14% for IGF-I and approximately 11.5% for IGFBP-3 over the entire study. Coefficients of variation varied significantly among individual QC subjects, ranging from 12.3% to 17.6% for IGF-I and 8.9% to 12.8% for IGFBP-3. Based on Levy-Jennings plots, approximately 5% of the plates used for IGF-I in the main study were out of compliance. Finally, location on a plate had small but significant effects on IGF-I level. Together, these results highlight the need for care in large studies of putative biomarkers for cancer risk and illustrate some probable sources of heterogeneity in past epidemiologic studies of the IGF axis and cancer.     

A Comparison of Circulating Immune Complexes, Pregnancy Associated β1-Macroglobulin and Galactosyltransferase as Tumour Markers for Ovarian Cancer

Serial blood samples have been obtained from 12 patients with ovarian cancer who were treated by surgery and, generally, chemotherapy or radiotherapy. Some achieved clinical remission, but the majority relapsed after variable time interval. Three potential tumour markers (Circulating Immune Complexes, Pregnancy Associated beta 1-Macroglobulin and Galactosyltransferase) have been studied longitudinally in serum for clinical correlation, predictive value, and biochemical 'lead time' to clinically detectable progression. None of the 3 offered any signal advantage over the others, and each showed an inconsistent relationship to observed disease status, with high levels indicating a poor outlook and the converse not true. Thus, since the 'lead time' is short, and reliability low, none of the compounds can be strongly commended as individual markers for ovarian cancer.     

Hematogenous spread as a mechanism for the generation of abdominal wound metastases following laparoscopy

Background: We designed this study to determine whether hematogenous spread has a role in the etiology of port site metastases following laparoscopic surgery. Methods: The study design had two parts. In experiment 1, two groups (n = 30) of male Dark Agouti rats were studied. Under general anesthesia, the first group (20 rats) underwent 15 mins of laparoscopic insufflation, followed by an injection of a suspension of 105 Dark Agouti mammary adenocarcinoma (DAMA) cells into the internal jugular vein and a further 15-mins period of insufflation. The laparoscopic ports were then removed, and the wounds were closed and marked. In the second group (n = 10), the procedure was identical except that a 2.5-cm midline laparotomy was performed 15 mins after the commencement of anesthesia and insufflation was not used. The laparotomy was closed in two layers. In experiment 2, one group (n = 4) was studied. The study protocol was identical to the first laparoscopic group except that a larger number of 106 DAMA cells were injected. All rats in both experiments were killed 15 days later, and the injection site, laparoscopy wounds, and laparotomy wound were examined histologically by a blinded histopathologist. Results: In experiment 1, one port site tumor was detected in the laparoscopic group and no wound metastases were found in the laparotomy group. Postoperative weight loss was significantly less in the laparoscopic group (p < 0.001). In experiment 2, no port site metastases were detected. Conclusion: Although hematogenous spread is a possible mechanism in the development of port site metastases, judging from the low number of port site metastases in this study as compared to previous reports using this tumor model, this mechanism is unlikely to be a major contributor to the problem of wound metastasis following laparoscopy.     

A randomized clinical trial of strength training in young people with cerebral palsy

This randomized clinical trial evaluated the effects of a home-based, six-week strength-training programme on lower limb strength and physical activity of 21 young people (11 females, 10 males; mean age 13 years 1 month, SD 3 years 1 month; range 8 to 18 years) with spastic diplegic cerebral palsy (CP) with independent ambulation, with or without gait aids; (Gross Motor Function Classification System levels I to III). Compared with the 10 controls, the 11 participants in the strength-training programme increased their lower limb strength (combined ankle plantarflexor and knee extensor strength as measured by a hand-held dynamometer) at 6 weeks (F(1,19)=4.58, p=0.046) and at a follow-up 12 weeks later (F(1,18)=6.25, p=0.041). At 6 weeks, trends were also evident for improved scores in Gross Motor Function Measure dimensions D and E for standing, running and jumping, and faster stair climbing. A relatively short clinically feasible home-based training programme can lead to lasting changes in the strength of key lower-limb muscles that may impact on the daily function of young people with CP.     

A qualitative analysis of the benefits of strength training for young people with cerebral palsy

This qualitative study investigated the positive and negative outcomes of a home-based strength-training programme for young people with cerebral palsy (CP). Eleven young people with spastic diplegic CP (seven females, four males; mean age 12 years 9 months, SD 2 years 10 months; range 8 to 18 years) and their parents were interviewed. Gross Motor Function Classification System scores ranged from I (walks without limitations) to III (walks with assistive device), with a mode of III. The strength-training programme, which was conducted in the participants' homes three times per week for 6 weeks (total of 18 prescribed sessions), comprised three exercises targeting the major support muscles of the lower limbs. Exercises were bilateral half squats, heel raises, and step-ups. The training load was increased by adding free weights to a backpack so that 8 to 10 repetitions of each exercise could be performed. Using thematic coding, three categories of outcome emerged: body function and structure, activity, and participation, which were influenced by environmental and personal contextual factors. The programme generated overwhelmingly positive outcomes with only minor negative responses about some equipment and the need for parental involvement. Benefits included perceptions that strength, flexibility, posture, walking, and the ability to negotiate steps had improved. In addition, participants reported psychological benefits such as a feeling of increased well-being and improved participation in school and leisure activities. The contextual factors highlighted the fact that sufficient clinician resources must be allocated to solve individual exercise and equipment problems. As well as providing further evidence that strength training can be beneficial, this study provides useful indicators to guide future quantitative studies of outcomes that are meaningful for people with CP.     

How Important Are Brain Banks for Alcohol Research?

This article contains the proceedings of a symposium at the 2002 RSA/ISBRA Meeting in San Francisco, organized and chaired by Clive Harper and co-chaired by Izuru Matsumoto. The presentations were (1) Introduction, by Clive Harper; (2) The quality of tissue-a critical issue, by Therese Garrick; (3) The first systematic brain tissue donor program in Japan, by Izuru Matsumoto; (4) Brain scans after death-really! by Adolf Pfefferbaum, Elfar Adalsteinsson, and Edith Sullivan; (5) Capture that (genial) expression, by Joanne Lewohl and Peter Dodd; and (6) Neurochemical/pharmacological studies: experimental design and limitations, by Roger Butterworth.     

Conjunctival squamous cell carcinoma with perineural invasion resulting in death.

Conjunctival squamous cell carcinoma is generally a low-grade malignancy. A 42-year-old man presented with histologic evidence of extra-tumoral perineural invasion associated with an incompletely excised limbal conjunctival squamous cell carcinoma. Despite further surgery, close observation, plaque radiotherapy, and eyelid-sparing orbital exenteration followed by external beam radiotherapy, the patient developed intracranial perineural invasion with involvement of the trigeminal and facial nerves, ultimately resulting in death. Repeated magnetic resonance imaging with contrast failed to detect perineural invasion until late in the course of disease. Awareness of the possibility of perineural invasion in patients with conjunctival squamous cell carcinoma and of its aggressive nature may be life-saving. Nevertheless, even with initial aggressive tumor control, some patients will show an aggressive tumor growth with recurrences.     

Genes involved in DNA repair and nitrosamine metabolism and those located on chromosome 14q32 are dysregulated in nasopharyngeal carcinoma.

Polymorphisms in nitrosamine metabolism, DNA repair, and immune response genes have been associated with nasopharyngeal carcinoma (NPC). Studies have suggested chromosomal regions involved in NPC. To shed light on NPC etiology, we evaluated host gene expression patterns in 31 NPC and 10 normal nasopharyngeal tissue specimens using the Affymetrix Human Genome U133 Plus 2.0 Array. We focused on genes in five a priori biological pathways and chromosomal locations. Rates of differential expression within these prespecified lists and overall were tested using a bootstrap method. Differential expression was observed for 7.6% of probe sets overall. Elevations in rate of differential expression were observed within the DNA repair (13.7%; P = 0.01) and nitrosamine metabolism (17.5%; P = 0.04) pathways. Differentially expressed probe sets within the DNA repair pathway were consistently overexpressed (93%), with strong effects observed for PRKDC, PCNA, and CHEK1. Differentially expressed probe sets within the nitrosamine metabolism pathway were consistently underexpressed (100%), with strong effects observed for NQ01, CYP2B6, and CYP2E1. No significant evidence of increases in rate of differential expression was seen within the immune/inflammatory pathway. A significant elevation in rate of differential expression was noted for chromosome 4p15.1-4q12 (13.0%; P = 0.04); both overexpression and underexpression were evident (38% and 62%, respectively). An elevation in the rate of differential expression on chromosome 14q32 was observed (11.3%; P = 0.06) with a consistent pattern of gene underexpression (100%; P < 0.0001). These effects were similar when excluding late-stage tumors. Our results suggest that nitrosamine activation and DNA repair are important in NPC. The consistent down-regulation of expression on chromosome 14q32 suggests loss of heterozygosity in this region.