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.

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.

LH in polycystic ovary syndrome: reproducibility and pulsatile secretion.

Serum concentrations of LH are increased in polycystic ovary syndrome (PCOS). We have investigated two aspects of LH secretion which have not previously been reported: its reproducibility within individuals and the pattern of superimposed pulses of LH secretion. In nine patients with PCOS the mean concentration of LH was calculated from 24 blood samples taken at 15-min intervals for 6 h on two or three occasions over 1 year. Results showed differences in mean LH between subjects but reproducible concentrations within subjects over that period. It has been shown that LH is secreted in a complicated pattern of superimposed pulses which can be characterized by using the statistical methods of time-series analysis. To evaluate these pulse patterns of LH we studied nine patients with PCOS and compared the results with those of 12 normal women in the early follicular phase of the ovarian cycle. Blood samples were taken at either 5-min intervals for 6 h of 1-min intervals for 1 h. Pulses were detected in both groups at frequencies of about 1 h and 2 to 3 min. There was no significant difference in the pulse frequencies between the patients and controls but the amplitude of both groups of pulses was increased in the PCOS patients.

Changes in plasma and whole blood lactate in response to arterial occlusion.

The development of lactic acidaemia in the adult forearm in response to partial and total arterial occlusion is described in both plasma and whole blood. Under conditions of total occlusion of the brachial artery lactate levels in the plasma compartment rise at a significantly faster rate; mean difference in gradients -11.6 95% confidence limits -15.6 and -7.6. Thus in these conditions they provide a more sensitive index of tissue hypoxia. Under conditions of partial occlusion there is no significant difference; mean difference in gradients 1.0 95% confidence limits 9.4 and -7.3. Though plasma lactate levels are more sensitive to the ischaemic state in certain circumstances, whole blood measurements are equally applicable to the monitoring of trends in blood lactic acid.

Maternal hemodynamics after normal delivery and delivery complicated by postpartum hemorrhage.

Serial hemodynamic investigations were performed in 40 women at 38 weeks' gestation and then 1, 2, 6, 10, and 14 days after normal delivery. Cardiac output was measured by Doppler and cross-sectional echocardiography at the aortic valve. In 30 controls who received an average of 280 mL intravenous fluid during labor, the mean cardiac output remained elevated (7.15 L/minute) for 24 hours after delivery and then fell to 5.39 L/minute at 10 days as a result of decreases in both heart rate and stroke volume. Blood pressure fell during the first 2 days after delivery and thereafter increased to values not significantly different from those recorded at the end of pregnancy. In ten women who experienced postpartum hemorrhage, stroke volume decreased and heart rate increased, relative to the control group, during the first 48 hours after delivery. Blood pressure and cardiac output, however, were not significantly different from values in the control group.

Third-generation cephalosporins for polymicrobial surgical sepsis.

During 31 months of study, 808 patients with polymicrobial surgical infection were randomized for antibiotic therapy between a third-generation cephalosporin (moxalactam disodium [149], cefotaxime sodium [125], and cefoperazone sodium [141]) and the combination of gentamicin sulfate plus clindamycin (393). Results based on antibiotic therapy included the following: cure in 83% given cephalosporin, 73% with antibiotic combination; control but recurrent sepsis in 7% and 15%; and failure in 4% and 8%, respectively. Such data support the tenet that third-generation cephalosporins are at least equal, if not superior, to the combination of gentamicin plus clindamycin for treatment of polymicrobial surgical sepsis.

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.

Effects of age and severity of illness on outcome and length of stay in geriatric surgical patients.

From April 1, 1990, to March 31, 1992, 8,899 patients who were 65 years of age and older underwent an anesthetic and surgical procedure in a 1,000-bed community hospital in Victoria, British Columbia, Canada. The hospital has been using a proprietary system called MedisGroups for assessing the severity of illness on admission and in-hospital morbidity. All patients were followed up until death or discharge from the hospital. Using the hospital database, we analyzed the patient sample to test the hypothesis that severity of illness was more important than age in predicting postoperative morbidity and mortality rates. Using correlation and multiple regression analysis, we found that the severity of illness was a much better predictor of outcome than age. The results were significant at the level of p < 0.001. Based on the results of this study, we recommend that age not be used in surgical decisions in the elderly.

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.

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.

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.

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.

The influence of thymectomy on Rous sarcoma regression.

The incidence of regression of wing-web tumors induced by Rous sarcoma virus was shown to be dependent on the quantity of thymus tissue remaining after neonatal thymectomy in chickens of inbred line 6. Frequency of metastasis was associated negatively with the amount of thymus tissue present. Tumor regression and metastasis restriction both appeared dependent on the quantity of thymic tissue present.