Total knee replacement survivorship by Design Philosophy: are we ignoring medial pivot design? Analysis based on the UK National Joint Registry.

The UK National Joint Registry(NJR) has not reported total knee replacement (TKR) survivorship based on design phi- losophy alone, unlike its international counterparts. We report outcomes of implant survivorship based on design phi- losophy using data from NJR's 2020 annual report. All TKR implants with an identifiable design philosophy from NJR data were included. Cumulative revision data for cruciate-retaining(CR), posterior stabilised(PS), mobile-bearing(MB) design philosophies was derived from merged NJR data. Cumulative revision data for individual brands of implants with the medial pivot (MP) philosophy were used to calculate overall survivorship for this design philosophy. The all-cause revision was used as the endpoint and calculated to 15 years follow-up with Kaplan-Meier curves. 1,144,384 TKRs were included. CR is the most popular design philosophy (67.4%), followed by PS(23.1%), MB (6.9%) and least commonly MP (2.6%). MP and CR implants showed the best survivorship (95.7% and 95.6% respectively) at 15 years which is statistically significant at, and beyond, 10 years. Observed survivorship was lower at all time points with the PS and MB implants (94.5% for both designs at 15 years). While all design philosophies considered in this study survive well, CR and MP designs offer statistically superior survivorship at and beyond 10 years. MP design performs better than CR beyond 13 years yet, remain the least popular design philosophy used. Publishing data based on knee arthroplasty design phi- losophy would help surgeons when making decisions on implant choice.

Impact of age and sex on neural cardiovascular responsiveness to cold pressor test in humans.

Prior longitudinal work suggests that blood pressure (BP) reactivity to the cold pressor test (CPT) helps predict hypertension; yet the impact of age and sex on hemodynamic and neural responsiveness to CPT remains equivocal. Forty-three young (21 ± 1yr, means ± SE) men (YM, n = 20) and women (YW, n = 23) and 16 older (60 ± 1yr) men (OM, n = 9) and women (OW, n = 7) participated in an experimental visit where continuous BP (finger plethysmography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded during a 3- to 5-min baseline and 2-min CPT. Baseline mean arterial pressure (MAP) was greater in OM than in YM (92 ± 4 vs. 77 ± 1 mmHg, P < 0.01), but similar in women (P = 0.12). Baseline MSNA incidence was greater in OM [69 ± 6 bursts/100 heartbeats (hb)] than in OW (44 ± 7 bursts/100 hb, P = 0.02) and lower in young adults (YM: 17 ± 3 vs. YW: 16 ± 2 bursts/100 hb, P < 0.01), but similar across the sexes (P = 0.83). However, when exposed to the CPT, MSNA increased more rapidly in OW (Δ43 ± 6 bursts/100 hb; group × time, P = 0.01) compared with OM (Δ15 ± 3 bursts/100 hb) but was not different between YW (Δ30 ± 3 bursts/100 hb) and YM (Δ33 ± 4 bursts/100 hb, P = 1.0). There were no differences in MAP with CPT between groups (group × time, P = 0.33). These findings suggest that OW demonstrate a more rapid initial rise in MSNA responsiveness to a CPT compared with OM. This greater sympathetic reactivity in OW may be a contributing mechanism to the increased hypertension risk in postmenopausal women.

Search for charged Higgs bosons in e+e- collisions at [Formula: see text].

A search is made for charged Higgs bosons predicted by Two-Higgs-Doublet extensions of the Standard Model (2HDM) using electron-positron collision data collected by the OPAL experiment at [Formula: see text], corresponding to an integrated luminosity of approximately 600 pb-1. Charged Higgs bosons are assumed to be pair-produced and to decay into [Formula: see text], τντ or AW±. No signal is observed. Model-independent limits on the charged Higgs-boson production cross section are derived by combining these results with previous searches at lower energies. Under the assumption [Formula: see text], motivated by general 2HDM type II models, excluded areas on the [Formula: see text] plane are presented and charged Higgs bosons are excluded up to a mass of 76.3 GeV at 95 % confidence level, independent of the branching ratio BR(H±â†’τντ ). A scan of the 2HDM type I model parameter space is performed and limits on the Higgs-boson masses [Formula: see text] and mA are presented for different choices of tanß.

The use of taxanes in choriocarcinoma; a case report and review of the literature.

BACKGROUND: Both preclinical data and case reports support the use of taxanes for high-risk metastatic choriocarcinoma. CASE: We report the case of a 31-year-old with metastatic choriocarcinoma who required 3rd-line treatment with a paclitaxel-cisplatin-based regimen. She achieved a complete response and remains relapse-free 21 months after her last dose of chemotherapy. CONCLUSION: The literature suggests that paclitaxel contributes significantly to the treatment of choriocarcinoma and its use should be explored further. This is the first case report formally reporting its combination with cisplatin.

Vestibular activation of sympathetic nerve activity.

AIM: The vestibulosympathetic reflex refers to sympathetic nerve activation by the vestibular system. Animal studies indicate that the vestibular system assists in blood pressure regulation during orthostasis. Although human studies clearly demonstrate activation of muscle sympathetic nerve activity (MSNA) during engagement of the otolith organs, the role of the vestibulosympathetic reflex in maintaining blood pressure during orthostasis is not well-established. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes indicates that it is a powerful and independent reflex. Ageing, which is associated with an increased risk for orthostatic hypotension, attenuates the vestibulosympathetic reflex. The attenuated reflex is associated with a reduction in arterial pressure. CONCLUSION: These findings suggest that the vestibulosympathetic reflex assists in blood pressure regulation in humans, but future studies examining this reflex in other orthostatically intolerant populations are necessary to address this hypothesis.

The delta and delta ' subunits of the DNA polymerase III holoenzyme are essential for initiation complex formation and processive elongation.

delta and delta' are required for assembly of the processivity factor beta(2) onto primed DNA in the DNA polymerase III holoenzyme-catalyzed reaction. We developed protocols for generating highly purified preparations of delta and delta'. In holoenzyme reconstitution assays, delta' could not be replaced by delta, tau, or gamma, even when either of the latter were present at a 10,000-fold molar excess. Likewise, delta could not be replaced by delta', tau, or gamma. Bacterial strains bearing chromosomal knockouts of either the holA(delta) or holB(delta') genes were not viable, demonstrating that both delta and delta' are essential. Western blots of isolated initiation complexes demonstrated the presence of both delta and delta'. However, in the absence of chipsi and single-stranded DNA-binding protein, a stable initiation complex lacking deltadelta' was isolated by gel filtration. Lack of delta-delta' decreased the rate of elongation about 3-fold, and the extent of processive replication was significantly decreased. Adding back delta-delta' but not chipsi, delta, or delta' alone restored the diminished activity, indicating that in addition to being key components required for the beta loading activity of the DnaX complex, deltadelta' is present in initiation complex and is required for processive elongation.

Rapid repair of titanium particle-induced osteolysis is dramatically reduced in aged mice.

Aseptic loosening is the most common cause of orthopaedic implant failure. This process is thought to be due to osteolysis induced by implant-derived wear particles. Teitelbaum and colleagues have recently developed a promising murine calvarial model of wear particle-induced osteolysis. However, prior to this study, this model had only been assessed qualitatively. We now report a reproducible, quantitative version of the calvarial model of wear particle-induced osteolysis, in which the extent of osteolysis (and repair) of entire parietal bones is assessed by histomorphometry of contact microradiographs. Using this model, we found that the osteolytic response is transient and rapidly repaired in one month old mice. The extent of osteolysis peaks 7 days after particle implantation and returns to baseline levels by 13 days. A similar amount of osteolysis and even more extensive repair is observed when particles are implanted repeatedly. In contrast, aged mice develop progressive osteolysis with no detectable repair. As a result, 26 month old mice have approximately 17-fold more osteolysis than one month old mice 21 days after particle implantation. Skeletally mature, adult mice (4-16 months old) show an intermediate pattern of response. Osteolysis in these mice peaks at 7 days after particle implantation but it is repaired more slowly than in the one month old mice. Taken together, these results underscore the role of an imbalance between bone resorption and bone formation in the development of aseptic loosening and suggest that agents that stimulate bone formation maybe useful in prevention or treatment of aseptic loosening.

Cognitive processing of multidimensional stimuli in schizophrenia: formal modeling of judgment speed and content.

This article presents a formal, mathematical account of relations between response times on simple cognitive tasks and content of complex judgments involving multiple stimulus dimensions for people with schizophrenia. Changes in multidimensional judgments were viewed as the result of interference from increased stages of encoding with respect to the individual dimensions. Information on dimensional properties encoded earlier in a judgment trial was considered to be more susceptible to loss over the rest of the trial, because of a larger number of encoding stages applied to the remaining dimensional properties. Model predictions were tested with samples of paranoid and nonparanoid schizophrenic participants and controls. Unidimensional encoding speed was assessed by reaction times in an explicit similarity ratings task, and multidimensional judgment content was assessed by the relative importance of different stimulus dimensions to participants' ratings in an implicit similarity ratings task. Results support validity of the model.

Transforming growth factor-alpha levels in the serum and ascites of patients with advanced epithelial ovarian cancer.

A variety of cytokines have been identified to play a role in ovarian cancer. In this pilot study, we sought to determine whether transforming growth factor-alpha (TGF-alpha) was detectable in the serum and ascites of women with advanced stage epithelial ovarian cancer. TGF-alpha was measured using an enzyme-linked immunosorbent assay and was present in 18 of 25 control sera. Prior to treatment for stage III or IV epithelial ovarian cancer, 18 patients had undetectable serum levels of TGF-alpha, while 18 had values ranging from 10.6 to 531.7 pg/ml. The group with undetectable levels had a 6-month greater median survival; detectable TGF-alpha might be a negative prognostic indicator. In a separate group undergoing second-look laparotomy, differences in median TGF-alpha values versus controls and the primary study group approached significance. TGF-alpha was detected in significantly more control peritoneal fluid samples than in patient ascites. A larger study is warranted.

Cervical tumor characterization by transvaginal color flow Doppler ultrasound.

The aim of the study was to investigate the blood flow characteristics of benign cervical lesions and invasive cervical tumors and to determine if invasive cervical tumors can be predicted by transvaginal sonography (TVS) and color flow Doppler (CFD). The study design incorporated an open prospective collection of data from patients attending the Women's Cancer Center, University of Minnesota and the Sydney Women's Cancer Center. Inclusion criteria included patients with known benign or malignant cervical pathology. The study group of 66 patients comprised 32 patients with invasive cervical cancer and 34 patients with benign cervical lesions. Benign cervixes were significantly more likely to have absent or normal flow whereas malignant lesions were significantly more likely to have abnormal or increased flow (P < 0.0001). No differences in the uterine or intratumor systolic, diastolic, or mean velocity were found between the two groups. A reduction in the uterine artery pulsatility index (PI) and resistance index (RI) from 1.84 to 1.55 and 0.73 to 0.71, respectively, and also in the intracervical PI from 1.5 to 1.1, in the benign compared to invasive group was found, none of which reached statistical significance. However the intracervical RI was statistically lower (0.62) in malignant tumors compared to patients with benign lesions (0.71) (P = 0.03). The effect of menopause on blood flow characteristics was variable and overall not significant. While the uterine artery systolic velocity was significantly higher in premenopausal women, no such effect was found for the diastolic or mean velocity or the PI and RI. In postmenopausal women, the intratumor PI and RI were higher compared to premenopausal women. In conclusion, transvaginal CFD analysis of the uterine arterial or intratumor bed does not appear to be beneficial in attempting to distinguish benign from malignant cervical tumors.

Histopathologic analysis of failed vascularized fibular grafts in femoral head osteonecrosis.

Salient histopathological features in 13 failed free vascularized fibular autografts implanted for osteonecrosis of the femoral head are documented. Of particular clinical and/or biomechanical relevance are 1-2-mm-thick seams of viable lamellar bone bonded circumferentially to anatomically intact but necrotic graft cortices, which appear to preclude their revascularization and remodeling. Surrounding the grafts are 3-6-mm-thick rings of reactive bone, fused in many sites (average approximately 54%) to the osseous seams. They consist of a layer of sclerotic cortical-like bone melded with an outer layer of thickened cancellous bone. This remodeled reactive bone, largely the result of drilling, appears to buttress the grafts structurally and by inference, functionally. Operative failures in all but one case are attributed primarily to collapse of the necrotic, fractured superior subtending segment of the graft and of the subchondral plate secondary to size and progression of the osteonecrosis and superimposed osteoarthrosis. Morphological integrity of grafts elsewhere and perifibular reactive sclerotic bone remain unimpaired for up to 5 1/2 years. The salutary features of vascularized autografts would appear to give them a decided advantage over their nonvascularized counterpart.

Cortical metastatic lesions of the appendicular skeleton from tumors of known primary origin.

BACKGROUND AND OBJECTIVES: Metastatic disease represents the most common neoplastic process involving bone. Recently, a small subset of cortical based metastatic lesions has been identified. We attempted to delineate the incidence, origin, location, and possible significance of these lesions within an orthopaedic patient population. METHODS: A chart and radiographic review of patients treated for metastatic disease to bone over a 17-year period was performed. Inclusion criteria for lesions were as follows: 1) an appendicular skeletal site, 2) histopathologic confirmation of origin, and 3) presence within a patient diagnosed with a single, known neoplastic process. The lesions were classified as either cortical or medullary based. RESULTS: Eighty-three lesions (70 patients) satisfied inclusion criteria. Most lesions were of pulmonary (26), breast (22), renal (16), or prostatic (8) tumor origin. Eighteen lesions (22%) from 15 patients were identified as cortical and represented initial presentation in 7 patients. These lesions were of pulmonary (11), renal (5), and breast (2) tumor origin. CONCLUSIONS: Cortical based metastases within the appendicular skeleton may occur more frequently than previously expected. While tumors of pulmonary and renal origin accounted for 42 of the 83 (51%) appendicular lesions, they were responsible for 16 of the 18 (89%) cortical metastases. This preponderance of pulmonary and renal metastases to the cortex is consistent with previously published reports. Our findings may be of value when diagnosing and treating patients whose initial presentation is a cortically based lesion.

The effect of prolonged cycles of chemotherapy on quality of life in gynaecologic cancer patients.

OBJECTIVE: The aim of this study was to determine if the prescription of prolonged cycles of chemotherapy to patients with a variety of gynaecologic cancers has an adverse effect on quality of life (QOL). METHODS: Patients attending a single gynaecologic oncology clinic who received greater than 6 cycles of chemotherapy were identified. Prior to each chemotherapy cycle, patients were asked to complete a modified Functional Assessment Cancer Therapy-General (FACT-G) quality of life form. QOL scores were compared to their baseline or pretreatment score (cycle 1 score), as well as to their score representing the completion of primary therapy (cycle 6 score). RESULTS: Seventeen patients were identified as having received greater than 6 cycles of systemic cytotoxic chemotherapy. The total number of chemotherapy cycles analyzed was 95. Comparing QOL scores for cycle 1 and 6 to cycles 7-16, we found no significant alteration (improvement or deterioration) in the following subscale scores: physical well being (PWB), social well being (SWB), and functional well being (FWB). Similarly, overall QOL as represented by the summed individual scores was also not affected by the prescription of up to 16 cycles of chemotherapy. Analysis of the emotional well being (EWB) subscale scores revealed a significant downward trend after the 12th cycle of therapy as compared to the 6th cycle (p = 0.04), however this trend was not significant when compared to the pretreatment or cycle 1 scores (p = 0.16). There was however a statistically significant progressive deterioration in the subscale score of the relationship with the doctor (RWD). This was most marked after the 10th cycle of therapy (p < 0.0001). When split by disease status, we again found no statistically significant alteration in PWB, SWB, RWD, EWB, FWB and overall QOL for cycle 1 and 6 as compared to cycles 7-17. However, those patients who were able to attain a complete clinical response (CCR) disease status, achieved a higher SWB (p = 0.003), RWD (p = 0.02), EWB (p = 0.03), and overall QOL scores (p = 0.04) while their PWB scores were not statistically different from patients with stable (p = 0.7) or progressive disease (p = 0.6). CONCLUSION: In conclusion, the prescription of prolonged cycles of chemotherapy to patients with gynaecologic cancers does not result in an overall deterioration of QOL. Further more an improvement in subscale and overall QOL was demonstrated in those patients able to attain a complete clinical response (CCR).

A simplified method for detubularization in the construction of a continent ileocolic reservoir (Miami pouch).

The development of continent urinary diversions was an important step forward in improving the quality of life of patients undergoing pelvic exenteration. While the technique is relatively simple, it can be very time-consuming and uses a significant portion of the patient's colon in its construction. Here a modification of the technique for construction of a continent ileocolic reservoir which results in a similar reservoir that uses less colon and requires less time to construct is presented. We also report results of the use of this technique in seven patients.

Primary retroperitoneal sarcomas: common symptoms, common diagnoses, uncommon disease.

Primary retroperitoneal sarcomas may present with symptoms and signs that mimic common musculoskeletal disorders of the extremities that are quite remote from the source of the problem. This often misleads the clinician and results in delays in diagnosis. The authors present 6 patients with retroperitoneal sarcoma who had a common or nonspecific orthopaedic condition of the extremity. Delays in diagnosis ranged from 2 to 30 months. No patient survived his or her tumor. Clinicians should be alerted to the possibility of a retroperitoneal tumor that presents primarily or initially with extremity signs and symptoms but with few or no clues of the presence of a localized sarcoma in the retroperitoneal space.

Osteoma of the long bones and the spine. A study of eleven patients and a review of the literature.

The clinical features, radiographic and histopathological findings, treatment, and results are described for eleven patients who were managed for an extracranial osteoma at our medical center between 1980 and 1993. Ten of the patients were initially seen because of dull, aching bone pain that had been present for two weeks to thirty years. Radiographs demonstrated single or multiple homogeneous, well defined, radiodense foci with smooth round or lobulated margins. The histopathological features consistently included uniformly dense, compact, cortical-like, mature lamellar bone. The preoperative diagnosis was unclear for all patients, and osteoma was rarely considered in the differential diagnosis. For four patients, a tentative diagnosis of osteosarcoma was made, and a wide excision was carried out in two of these patients. Marginal excision with less than three millimeters of normal tissue around the lesion was performed in most patients. None of the osteomas recurred, and ten patients had relief of the pain. Awareness of the clinical, radiographic, and histopathological features of osteoma, as described, is valuable for making a differential diagnosis and for distinguishing osteomas from other lesions.

Gynecologic reconstruction with a rectus abdominis myocutaneous flap: an update.

This series reports the outcomes and significant complications associated with the rectus myocutaneous flap when used for pelvic or inguinal reconstruction in patients with gynecologic cancers. Perioperative variables were retrospectively reviewed to identify social and medical risk factors as well as intraoperative and postoperative complications that predisposed to rectus flap failure. Fifteen patients with gynecologic malignancies underwent reconstructive procedures using a vertically oriented rectus abdominis myocutaneous flap for either vaginal (n = 14) or inguinal (n = 1) reconstruction. The patients' primary cancers were cervical (n = 11), rectal (n = 1), ovarian (n = 1), vulvar (n = 1), and vaginal (n = 1). The median age was 50 years. The median follow-up was 17 months. All flaps were mobilized in conjunction with a radical salvage operation. There were no cases of vaginal prolapse and no abdominal wound infections. However, 4 patients (27%) had major postoperative morbidity in this small series. There was one wound dehiscence and three episodes of necrosis of the subcutaneous and cutaneous portions of the flap. All 4 of these patients required additional operative intervention or debridement. Eleven patients had complete healing of the flap. The rectus abdominis myocutaneous flap is a valuable option for gynecologic reconstructive procedures. Perioperative strategies for improving flap viability include the identification of risk factors that may compromise flap perfusions such as prior abdominal incisions, peripheral vascular disease, and obesity. Meticulous surgical technique is required to preserve the vascular pedicle. These strategies may be useful in preoperative counseling, the perioperative evaluation, and the intraoperative management.