Extent of recovery in the first 12 months of complex regional pain syndrome type-1: A prospective study.

BACKGROUND: The literature concerning the outcomes of complex regional pain syndrome (CRPS) is contradictory, with some studies suggesting high rates of symptom resolution, whilst others demonstrate that CRPS symptoms can persist and lead to significant disability. The aim of the present study was to carefully document the extent of recovery from each of the signs and symptoms of CRPS. METHODS: A sample of 59 patients with recently onset (<12 weeks) CRPS-1 were followed prospectively for 1 year, during which time they received treatment-as-usual. At baseline, 6 and 12 months, the following were measured: CRPS severity scores (symptoms and signs of CRPS), pain, disability, work status and psychological functioning. RESULTS: Analyses showed that rates of almost all signs and symptoms of CRPS reduced significantly over 1 year. Reductions in symptom severity were clinically relevant and were greatest in the first 6 months and plateaued thereafter. However, at 1 year, nearly 2/3 of patients continued to meet the IASP-Orlando criteria for CRPS and 1/4 met the Budapest research criteria for CRPS. Only 5.4% of patients were symptom-free at 12 months. CONCLUSIONS: Overall the results were less optimistic than several previously conducted prospective studies and suggest that few cases of CRPS resolve completely within 12 months of onset. Improvements were generally greater in the first 6 months, and suggest that it may be worth exploring early interventions to prevent long-term disability in CRPS.

Economic evaluation in chronic pain: a systematic review and de novo flexible economic model.

There is unmet need in patients suffering from chronic pain, yet innovation may be impeded by the difficulty of justifying economic value in a field beset by data limitations and methodological variability. A systematic review was conducted to identify and summarise the key areas of variability and limitations in modelling approaches in the economic evaluation of treatments for chronic pain. The results of the literature review were then used to support the development of a fully flexible open-source economic model structure, designed to test structural and data assumptions and act as a reference for future modelling practice. The key model design themes identified from the systematic review included: time horizon; titration and stabilisation; number of treatment lines; choice/ordering of treatment; and the impact of parameter uncertainty (given reliance on expert opinion). Exploratory analyses using the model to compare a hypothetical novel therapy versus morphine as first-line treatments showed cost-effectiveness results to be sensitive to structural and data assumptions. Assumptions about the treatment pathway and choice of time horizon were key model drivers. Our results suggest structural model design and data assumptions may have driven previous cost-effectiveness results and ultimately decisions based on economic value. We therefore conclude that it is vital that future economic models in chronic pain are designed to be fully transparent and hope our open-source code is useful in order to aspire to a common approach to modelling pain that includes robust sensitivity analyses to test structural and parameter uncertainty.

A geophysical shock and air blast simulator at the National Ignition Facility.

The energy partitioning energy coupling experiments at the National Ignition Facility (NIF) have been designed to measure simultaneously the coupling of energy from a laser-driven target into both ground shock and air blast overpressure to nearby media. The source target for the experiment is positioned at a known height above the ground-surface simulant and is heated by four beams from the NIF. The resulting target energy density and specific energy are equal to those of a low-yield nuclear device. The ground-shock stress waves and atmospheric overpressure waveforms that result in our test system are hydrodynamically scaled analogs of full-scale seismic and air blast phenomena. This report summarizes the development of the platform, the simulations, and calculations that underpin the physics measurements that are being made, and finally the data that were measured. Agreement between the data and simulation of the order of a factor of two to three is seen for air blast quantities such as peak overpressure. Historical underground test data for seismic phenomena measured sensor displacements; we measure the stresses generated in our ground-surrogate medium. We find factors-of-a-few agreement between our measured peak stresses and predictions with modern geophysical computer codes.

Mechanical prophylaxis of deep-vein thrombosis after total hip replacement a randomised clinical trial.

Routine prophylaxis for venous thromboembolic disease after total hip replacement (THR) is recommended. Pneumatic compression with foot pumps seems to provide an alternative to chemical agents. However, the overall number of patients investigated in randomised clinical trials has been too small to draw evidence-based conclusions. This randomised clinical trial was carried out to compare the effectiveness and safety of mechanical versus chemical prophylaxis of DVT in patients after THR. Inclusion criteria were osteoarthritis of the hip and age less than 80 years. Exclusion criteria included a history of thromboembolic disease, heart disease, and bleeding diatheses. There were 216 consecutive patients considered for inclusion in the trial who were randomised either for management with the A-V Impulse System foot pump. We excluded 16 patients who did not tolerate continuous use of the foot pump or with low-molecular-weight heparin (LMWH). Patients were monitored for DVT using serial duplex sonography at 3, 10 and 45 days after surgery. DVT was detected in three of 100 patients in the foot-pump group and with six of 100 patients in the LMWH group (p < 0.05). The mean post-operative drainage was 259 ml in the foot-pump group and 328 ml in the LMWH group (p < 0.05). Patients in the foot-pump group had less swelling of the thigh (10 mm compared with 15 mm; p < 0.05). One patient developed heparin-induced thrombocytopenia. This study confirms the effectiveness and safety of mechanical prophylaxis of DVT in THR. Some patients cannot tolerate the foot pump.

Evaluation of feasibility and accuracy of sentinel node biopsy in early breast cancer.

BACKGROUND: Current literature has suggested that sentinel node biopsy may eventually replace axillary dissection as the nodal staging procedure of choice in early breast cancer. The goals of our study were to determine the accuracy of the sentinel node in predicting axillary nodal status and to evaluate the feasibility of incorporating sentinel node biopsy into a general surgical practice. METHODS: Between June 1999 and August 2000, 158 clinically node negative women with a histological diagnosis of T1 or T2 breast cancer were enrolled in the study. Both technetium sulfur colloid radiotracer and isosulfan blue dye were used to guide sentinel node biopsy. Sentinel node biopsy was always followed by a complete axillary dissection. The histopathology of sentinel nodes using serial sectioning and cytokeratin immunohistochemistry was compared with that of the nonsentinel nodes evaluated with routine hematoxylin and eosin stain. RESULTS: The overall sentinel node detection rate was 84% (89 of 106 patients). Sentinel node biopsy was most successful when a combination of radiotracer and dye was used. The staging accuracy of sentinel node biopsy was 98% (87 of 89); the sensitivity of the method was 94% (34 of 36); the false negative rate was 6% (2 of 36); the negative predictive value was 96% (53 of 55); and the rate of metastases to the sentinel node only was 56% (20 of 36). The results varied considerably among surgeons. CONCLUSIONS: The findings in our study support the hypothesis that the sentinel node is an accurate predictor of axillary nodal status in women with early breast cancer. These results suggest that the excellent findings in the literature can be reproduced by a group of general surgeons in a community-based hospital.

An analysis of breast cancer surgery after free transverse rectus abdominis myocutaneous (TRAM) flap reconstruction.

BACKGROUND: Breast reconstruction is currently offered on a more routine basis to patients after mastectomy for breast cancer. This paper analyzes the outcomes of breast cancer surgery, and the results and effects of breast reconstruction using free TRAM flaps. METHODS: A retrospective review of 75 consecutive patients who had free transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction after breast cancer surgery was performed. A total of 92 free TRAM flaps were performed on 75 patients in Victoria, British Columbia, from January 1992 to May 1999. Thirty-three patients (44%) underwent primary breast cancer surgery and an immediate reconstruction (7 bilateral and 27 unilateral) and 42 patients (56%) had delayed reconstruction (10 bilateral and 32 unilateral). RESULTS: Twenty- one patients (28%) had stage 0 disease, 20 (26.7%) had stage I disease, 17 (22.7%) had stage IIA disease, 12 (15%) had stage IIB disease, and 4 (5.3%) had stage IIIA disease. In 1 patient the stage of disease was unknown. The mean patient age was 49.4 years (range 33 to 73). Of the patients undergoing immediate reconstruction 3 had postoperative chemotherapy and 1 had postoperative radiotherapy. Three patients had combined chemoradiotherapy. In none of these cases was the adjuvant therapy delayed by the reconstructive surgery. Overall mean follow-up time from cancer diagnosis was 56.8 months and from the time of TRAM flap reconstruction, 36.7 months. To date, 5 recurrences have been detected (6.6%). Mean time between reconstruction and detection of recurrence was 22.8 months. Detection of recurrence was achieved clinically and was not impaired in any of the cases by the presence of the free flap. Patient satisfaction was assessed via a telephone survey, with 93% of patients pleased with the cosmetic results of their surgery. CONCLUSIONS: For those patients with breast cancer requiring mastectomy, free TRAM flap reconstruction is a safe, cosmetically acceptable surgical alternative that impairs neither effective breast cancer surgery nor detection of recurrent disease.

Expression of the cyclic AMP-dependent transcription factors, CREB, CREM and ATF2, in the human myometrium during pregnancy and labour.

Elevated concentrations of cyclic AMP (cAMP) in the human myometrium may promote uterine quiescence during pregnancy by protein kinase A (PKA)-mediated phosphorylation and subsequent inactivation of myosin light-chain kinase, as well as by the phosphorylation and activation of cAMP-dependent transcription factors. In this context, we show that the altered expression of cAMP response-element binding protein (CREB), cAMP response-element modulator protein (CREM) and activating transcription factor 2 (ATF2) are implicated in the maintenance of myometrial quiescence during fetal maturation and the switch to uterine activation at term. Using electrophoretic mobility shift and super shift assays, as well as immunoblotting of paired myometrial tissue samples from non-pregnant, pregnant non-labouring and spontaneous labouring women, we defined the patterns of expression of various isoforms of these proteins in the human uterus. Here, we report spatio-temporal changes in the expression of a 43 kDa form of CREB, a 28 kDa CREM-like protein, and a novel 28 kDa ATF2-like protein which are differentially expressed, depending on the gestational state of the uterus. Changes in the pattern of expression of these potent transcription factors may have an important role in the control of uterine activity throughout pregnancy.

Recurrence and survival after surgical management of rectal cancer.

BACKGROUND: Reported local recurrence rates for rectal cancer are significantly reduced using a combination of superior surgical technique, in the form of total mesorectal excision, and routine radiotherapy. In an attempt to determine the effectiveness of current local management strategies, a review of Vancouver Island Cancer Centre patients with rectal cancer was performed and the overall local recurrence rate was identified. METHODS: We retrospectively reviewed the charts of 272 rectal cancer patients from 1988 to 1998. Two hundred and twenty-nine patients met inclusion criteria. Analysis of patient factors included age, gender, type of surgery, and adjuvant therapy. Tumors were assessed for level, stage, and grade. Local recurrence and distant metastases were also documented. Variables influencing local recurrence in this group were identified and disease-free and actuarial survival determined. RESULTS: Of 229 patients analyzed, 12.7% (29) had local recurrences. Variables influencing local recurrence were number of positive lymph nodes, vascular invasion, and neural invasion. There was no significant difference in local recurrence between patients having anterior resection and those having abdominoperineal resection. None of the patients who received preoperative radiotherapy had a local recurrence. Actuarial disease-free survival was 87% at 5 years. CONCLUSIONS: Limiting local recurrence is one of the most important goals in the treatment of rectal cancer. It is essential to identify those patients with "high risk" tumors as identified by endorectal ultrasound or pathologic features. These patients comprise the group most likely to benefit from a routine mesorectal excision combined with adjuvant radiotherapy.

Gestational changes in the levels of transforming growth factor-beta1 (TGFbeta1) and TGFbeta receptor types I and II in the human myometrium.

As term approaches, a number of key proteins [contraction-associated proteins (CAPs)] are expressed within the human myometrium that are essential for the activation of powerful coordinated contractions during labor. The nature of the signals that switch on the synthesis of CAPs in vivo is not known. The ryanodine-sensitive intracellular Ca2+ release channel (RyR2) is a CAP whose expression in vitro is activated by transforming growth factor-beta (TGFbeta). The present experiments were performed to determine whether TGFbeta and TGFbeta receptors are present in the human myometrium at term and to explore the idea that they might form part of a signaling system in vivo. TGFbeta receptor types I and II, but not III, were demonstrated in myometrial smooth muscle in tissue taken from nonpregnant, pregnant nonlaboring, and spontaneous laboring women. Western blotting was used subsequently to determine the relative expression of TGFbeta receptor types I and II. Using nonpregnant myometrium as a baseline control the levels of expression of receptor types I and II were significantly increased by 168 +/- 19% (n = 6) and 162 +/- 22% (n = 7) in pregnant nonlaboring myometrium. In spontaneous laboring myometrium the levels of TGFbeta receptor type I and II expression were 93 +/- 12% (n = 6) and 85 +/- 11% (n = 7), respectively, compared to nonpregnant control values and were significantly lower than levels in pregnant nonlaboring tissues. The total TGFbeta1 levels in the myometrial tissues were 334 +/- 10, 534 +/- 73, and 674 +/- 106 pg/g tissue wet wt in nonpregnant, pregnant nonlaboring, and spontaneous laboring myometrium (n = 3 in each group), respectively. Thus, the TGFbeta signaling system appears to be up-regulated in the myometrium before the onset of parturition. The apparent loss of receptors in the spontaneous laboring samples in the presence of elevated total levels of TGFbeta may be indicative of agonist-induced receptor down-regulation. These observations support the idea that cytokines, in particular TGFbeta1, may play a role in the normal processes that prepare the myometrium for parturition at term.

The responsiveness of isolated human hand vein endothelial cells in normal pregnancy and in pre-eclampsia.

1. Human hand vein endothelial cells were isolated from blood obtained by traumatic venepuncture. Cells were identified as endothelial by staining with endothelium-specific antibodies. The subject groups studied were (i) non-pregnant, (ii) pregnant (mean, 35 weeks gestation) and (iii) pre-eclamptic women (mean, 36 weeks gestation). 2. Fura-2 was used to measure agonist-induced responses in intracellular Ca2+ in single endothelial cells isolated and maintained in vitro. All of the cells examined responded to adenosine triphosphate (ATP) with a large transient increase in Ca2+ followed by a sustained plateau. 3. The responses to ATP were significantly larger in the cells from pregnant women than in those from non-pregnant and pre-eclamptic women, but no other differences were observed. The amplitudes of the responses to ATP were (means +/- s.e.m.) 0.56 +/- 0.04, 1.42 +/- 0.24 and 0.65 +/- 0.09 fura-2 ratio units for cells from non-pregnant, pregnant and pre-eclamptic subjects, respectively. 4. In cells isolated from non-pregnant subjects, the amplitude of the responses to carbachol, histamine and bradykinin were all smaller than those activated by ATP: 5.1, 13.9 and 4.4 %, respectively. Not all cells responded to these agonists: 25 % responded to carbachol, 70.5 % responded to histamine and 12.5 % responded to bradykinin. Sixty-five per cent of the cells from normotensive pregnant subjects responded to bradykinin compared with 25 % in the non-pregnant and 13.9 % in the pre-eclamptic subjects. 5. These data suggest that there may be differences in the responsiveness of venous endothelial cells in pregnancy and that pre-eclamptic cells behave differently.

Differential expression of ryanodine receptor RyR2 mRNA in the non-pregnant and pregnant human myometrium.

We describe here the expression of the ryanodine receptor isoforms RyR2 and RyR3 in human non-pregnant and pregnant (non-labouring) myometrium, and in isolated cultured myometrial cells. The mRNA encoding the RyR3 isoform was found in both non-pregnant and pregnant myometrial tissue samples; however, the mRNA for RyR2 was found only in pregnant samples. It can be speculated that the appearance of this additional isoform in the pregnant myometrium may increase the ability of this tissue to contract at term. Control of expression of the RyR2 gene may therefore be another example of an up-regulated signalling system in pregnancy. Although the mRNA for RyR3 was expressed in cultured myometrial cells, the mRNA for RyR2 could not be detected. Thus cultured myometrial cells appear to be similar to the non-pregnant myometrium. The cytokine transforming growth factor beta (TGF-beta) has been reported to alter RyR mRNA expression in many cell types. After treatment with TGF-beta, both RyR2 and RyR3 mRNAs could be detected in cultured myometrial cells. These observations support the idea that the expression of the RyR2 isoform is up-regulated both in pregnancy and in TGF-beta-treated cultured myometrial cells. Using measurements of 45Ca2+ release, we have further demonstrated that cultured human myometrial cells show a significant augmentation of both the Ca2+-induced Ca2+ release (CICR) mechanism and ryanodine-induced Ca2+ release after treatment with TGF-beta. Additionally, caffeine was able to induce Ca2+ release and sensitize the CICR mechanism to ryanodine. Thus we suggest that the appearance of RyR2 mRNA leads to the expression of this receptor/channel protein with identifiable pharmacological characteristics. These results are discussed in the context of the potential role of gene activation in the process of maturation of the human myometrium during pregnancy.

Benign mixed tumour of the vagina: an unusual cause for postmenopausal bleeding.

The authors report an unusual case of post-menopausal bleeding in the form of a benign mixed tumour of the vagina.

Erythrocyte ion and water balance and membrane potential in the puerperium of normal pregnancy.

OBJECTIVE: To examine the balance of erythrocyte ions and water during the rapid changes in plasma osmolality in the early puerperium, and during the subsequent period of sustained readjustment. DESIGN: A serial study from the third trimester of pregnancy to 20 weeks after delivery. PARTICIPANTS: Thirty-five primiparous women who had experienced no antenatal complications. MAIN OUTCOME MEASURES: Plasma osmolality, erythrocyte hydration, potassium, chloride and sodium were measured and nondiffusible ion content and erythrocyte membrane potential calculated. Plasma sodium, potassium and chloride were also measured. RESULTS: During the first week after delivery plasma osmolality increased (280 (SEM 0.52)-289 (SEM 0.64) mosmol/kg; P < 0.001) but erythrocyte hydration did not decrease (2.060 (SEM 0.018)-2.067 (SEM 0.021) 1/kg dry cells) because of an increase in total cell osmole content (577 (SEM 5.31)-597 (SEM 6.15) mosmol/kg dry cells; P = 0.001). This increase included nondiffusible anions, chloride and potassium. These changes in ionic balance did not affect membrane potential. After the first week of the puerperium and up to the 20th week, plasma osmolality was stable but erythrocyte osmole content and hydration both decreased. This was due to a decrease in nondiffusible anions and potassium with a smaller increase in chloride leading to a decrease in membrane potential (-14.31 (SEM 0.34)mV to -12.66 (SEM 0.28)mV; P < 0.001). CONCLUSIONS: A rapid increase in intracellular osmoles can occur in the mature erythrocyte and probably precedes the decrease in plasma osmolality in the puerperium. Changes in erythrocyte homeostasis in the first week of the puerperium can be accounted for by alterations in nondiffusible anions. After the first week of the puerperium it appears that the functional organisation of the membrane is changing.