Neovascularisation in de Quervain’s disease of the wrist: novel combined therapy using sclerosing therapy with polidocanol and eccentric training of the forearms and wrists—a pilot report

De Quervain's disease has been described as an entrapment of the extensor pollicis brevis and abductor pollicis tendons in the first dorsal compartment of the wrist is a common cause of wrist and hand pain. Currently, intrasheath corticosteroid injections have been reported to be successful as well as surgical release of the first dorsal compartment. We report on three female recreational athletes (median age 57 years, pain VAS 7/10) where we found significant neovascularisation of the extensor retinaculum using Power-Doppler sonography, which was not evident among subjects without de Quervain's disease of the wrist. Polidocanol sclerosing therapy (0.25% 1 ml) was performed with consecutive eccentric training (Thera-Band Flex-Bar, 6 x 15 repetitions of the forearm and wrist extensors and flexors daily). Four weeks later two patients had a resolution of their pain levels (DASH 61 vs. 27, p < 0.05) with resolution of the neovascularisation, while one patient underwent surgery despite pain reduction (6 to 2) 3 weeks following sclerosing therapy. Neovascularisation has been found in de Quervain's disease of the wrist using Power Doppler sonography. Combined treatment with Power Doppler controlled sclerosing therapy with consecutive eccentric training led to encouraging pilot results in terms of pain reduction and functional improvement within 1 month of therapy. A prospective randomized controlled trial is warranted to answer the question whether the sclerosing therapy, the eccentric training or the combination of both is beneficial in de Quervain's disease of the wrist.     

Lack of Analgesia by Oral Standardized Cannabis Extract on Acute Inflammatory Pain and Hyperalgesia in Volunteers

Background: Cannabinoid-induced analgesia was shown in animal studies of acute inflammatory and neuropathic pain. In humans, controlled clinical trials with [DELTA]9-tetrahydrocannabinol or other cannabinoids demonstrated analgesic efficacy in chronic pain syndromes, whereas the data in acute pain were less conclusive. Therefore, the aim of this study was to investigate the effects of oral cannabis extract in two different human models of acute inflammatory pain and hyperalgesia.

Methods: The authors conducted a double-blind, crossover study in 18 healthy female volunteers. Capsules containing [DELTA]9-tetrahydrocannabinol-standardized cannabis extract or active placebo were orally administered. A circular sunburn spot was induced at one upper leg. Heat and electrical pain thresholds were determined at the erythema, the area of secondary hyperalgesia, and the contralateral leg. Intradermal capsaicin-evoked pain and areas of flare and secondary hyperalgesia were measured. Primary outcome parameters were heat pain thresholds in the sunburn erythema and the capsaicin-evoked area of secondary hyperalgesia. Secondary measures were electrical pain thresholds, sunburn-induced secondary hyperalgesia, and capsaicin-induced pain.

Results: Cannabis extract did not affect heat pain thresholds in the sunburn model. Electrical thresholds (250 Hz) were significantly lower compared with baseline and placebo. In the capsaicin model, the area of secondary hyperalgesia, flare, and spontaneous pain were not altered.     

Evaluation of tibial component angles in 79 consecutive total knee arthroplasties

The tibial component angles (TCAs) were measured from the post-operative radiographs of 79 consecutive total knee arthroplasties (TKRs) to determine the prevalence of tibial component malposition. The mean TCA was 86.88° (S.D.±2.84°). Thirty-eight (48%) of the TKRs had TCAs of less than 87° and were therefore positioned in an unacceptable degree of varus. Such a high proportion of malorientated tibial components may compromise clinical results.     

The possible macroeconomic impact on the UK of an influenza pandemic

Little is known about the possible impact of an influenza pandemic on a nation's economy. We applied the UK macroeconomic model ‘COMPACT’ to epidemiological data on previous UK influenza pandemics, and extrapolated a sensitivity analysis to cover more extreme disease scenarios. Analysis suggests that the economic impact of a repeat of the 1957 or 1968 pandemics, allowing for school closures, would be short‐lived, constituting a loss of 3.35 and 0.58% of GDP in the first pandemic quarter and year, respectively. A more severe scenario (with more than 1% of the population dying) could yield impacts of 21 and 4.5%, respectively. The economic shockwave would be gravest when absenteeism (through school closures) increases beyond a few weeks, creating policy repercussions for influenza pandemic planning as the most severe economic impact is due to policies to contain the pandemic rather than the pandemic itself. Accounting for changes in consumption patterns made in an attempt to avoid infection worsens the potential impact. Our mild disease scenario then shows first quarter/first year reductions in GDP of 9.5/2.5%, compared with our severe scenario reductions of 29.5/6%. These results clearly indicate the significance of behavioural change over disease parameters. Copyright © 2009 John Wiley & Sons, Ltd.     

Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening

High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Treatment is not uniform, with some patients undergoing primary debulking surgery followed by chemotherapy (PDS) and others being treated directly with chemotherapy and only having surgery after three to four cycles (NACT). Which strategy is optimal remains controversial. We developed a mathematical framework that simulates hierarchical or stochastic models of tumor initiation and reproduces the clinical course of HGSC. After estimating parameter values, we infer that most patients harbor chemoresistant HGSC cells at diagnosis and that, if the tumor burden is not too large and complete debulking can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. These predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management.

Ovarian cancer is the eighth most common cancer and cancer death in women worldwide (1). High-grade serous tubo-ovarian cancer (HGSC) constitutes ∼70% of all ovarian malignancies and has the worst prognosis (2). Current treatment of most patients with HGSC consists of cytoreductive surgery and combination chemotherapy with platinum-containing DNA–cross-linking drugs and taxane-based microtubule-stabilizing agents (2). Although treatment significantly improves survival, most women relapse with chemotherapy-refractory disease and eventually succumb (3). Multiple mechanisms of chemoresistance have been documented (4, 5), including reduced intracellular drug accumulation (6), detoxification by increased levels of glutathione (7), altered DNA damage repair (8, 9), dysfunctional apoptotic pathways (10, 11), and hyperactivation of various cell signaling pathways (12–14). These mechanistic studies are consistent with recent genomic analyses that reveal marked clonal evolution of HGSC during therapy (15). Other evidence, however, supports a hierarchical organization of HGSC, featuring intrinsically chemoresistant “cancer stem cells” (CSCs) that can escape initial treatment and seed recurrence (16–18).Although there is uniform agreement that HGSC patients should receive surgery and chemotherapy, the optimal order and timing of these modalities remain controversial. Two main options exist: primary debulking surgery with adjuvant chemotherapy (PDS), or neoadjuvant chemotherapy, followed by interval debulking surgery (NACT) (19–24). In either case, the surgical standard of care is to seek maximal cytoreduction, with the objective being to leave no visible residual disease. However, the precise definition of such “optimal debulking” can vary among different centers, surgeons, and reports (19, 21, 24, 25).Several studies have found similar outcomes after PDS or NACT, including two highly influential randomized trials (EORTC and CHORUS) carried out across multiple countries (22, 23, 26–28). In both trials, however, the question of potential bias in patient recruitment has been raised, favoring potentially those with more extensive disease, who are less likely benefit from “upfront” surgery (23, 28). Consistent with this interpretation, overall survival in these trials was significantly shorter than that seen in other HGSC cohorts (19, 24, 29, 30). Closer examination of these reports reveals additional factors that might have influenced their conclusions. The EORTC study had inconsistencies in optimal debulking rates between participating centers, with the PDS-associated complete debulking data highly influenced by the results from a single institution (23). The CHORUS study involved 76 clinical sites, and there were substantial differences in surgery execution and chemotherapy drug selection/dosage between them (28).At Princess Margaret Cancer Center, retrospective data showed that PDS patients with no visible disease postresection survived substantially longer (7-y survival, >60%) than those receiving NACT (7-y survival, ∼10%). Furthermore, although residual tumor postresection is a critical determinant of survival, its influence on the PDS group was far more dramatic than on NACT group (24). Of course, this report suffers from deficiencies common to all retrospective analyses, including lack of randomization to account for tumor burden at diagnosis and other factors; indeed, the NACT group in this study did have more extensive disease.Another controversy in HGSC management focuses on the potential benefit of earlier diagnosis. Earlier diagnosis of primary HGSC is generally assumed to enhance patient survival and quality of life (3). Intuitively, one might predict that the same reasoning would apply to recurrent disease; however, survival is similar in relapsed patients treated earlier, based on increasing serum CA125 levels, than in those treated only when physical symptoms of recurrence appear (31). Conceivably, the lead time between CA125 rise and clinical recurrence is too short for earlier chemotherapy to be beneficial; if so, then patient survival might be extended by more sensitive methods, such as testing for circulating tumor DNA (ctDNA) (32, 33).To address these issues, we developed a mathematical framework that models the dynamics of HGSC progression, response to surgery and chemotherapy, and recurrence. Our results, generated over a wide range of parameters and accounting for hierarchical and stochastic models of tumor initiation, argue that PDS is superior to NACT when complete debulking is feasible and suggest that, with currently available therapies, the benefits of earlier detection are intrinsically restricted to primary HGSC.     

Partners in Planning. Information, Participation and Empowerment: Susan B. Rifkin and Pat Pridmore, Macmillan Education Ltd, London, 2001

The central thesis of this book is succinctly expressed (morethan once) in this aphorism: ‘Information is KNOWLEDGE,knowledge is POWER, sharing knowledge is EMPOWERMENT’.This rather neatly captures the great strengths of the book,and also its limitations. First, the strengths. As a handbook for people wanting to extendtheir repertoire of techniques in participatory planning—orwanting to get involved for the first time—one could hardlywish for     

Dietary treatment of atherosclerosis abolishes hyperresponsiveness to serotonin: implications for vasospasm

Diet-induced atherosclerosis in primates impairs vasodilator responses and greatly potentiates vasoconstrictor responses to serotonin. Serotonin may play an important role in the pathogenesis of vasospasm. In diet-induced regression of atherosclerosis, intimal lesions are reduced, but maximal vasodilator responses do not improve, perhaps because of vascular fibrosis. Our goal was to determine whether dietary treatment of atherosclerosis reverses the augmented vasoconstrictor responses to serotonin and thus might reduce susceptibility to vasospasm. Normal cynomolgus monkeys, atherosclerotic monkeys, and atherosclerotic monkeys that were given a normal (regression) diet for 18 months were studied. Morphometric studies indicated that the regression diet reduced lesions in the iliac and femoral artery since intimal area was reduced by about 50%. In the hind limb perfused at constant flow, residual resistance during maximal vasodilatation produced by infusion of adenosine tended to be greater in atherosclerotic monkeys than in normals and failed to improve in regression monkeys. In contrast, vasoconstrictor responses to serotonin were greatly potentiated in atherosclerotic monkeys and were restored to normal in regression monkeys. Serotonin (20 micrograms i.a.) decreased hind limb resistance (in mm Hg/ml/min) 0.34 +/- 0.06 (mean +/- SE) in normal monkeys, increased resistance 0.58 +/- 0.17 in atherosclerotic monkeys (p less than 0.05 vs. normal), and decreased resistance 0.70 +/- 0.15 in regression monkeys (p less than 0.05 vs. atherosclerotic). Thus, dietary treatment of atherosclerosis abolishes augmented vasoconstrictor responses to serotonin. It is proposed that treatment of atherosclerosis may be beneficial, even when vasodilator responses fail to improve, by reducing susceptibility to serotonin-induced vasospasm.     

Migraine and stripe-induced visual discomfort

We investigated stripe-induced visual discomfort and its relation to migraine. Some people find viewing striped patterns aversive. Prior work has suggested that migraineurs, in particular, are bothered by stripes. Subjects were selected by opportunity sampling. They were shown striped patterns and asked questions about their general health and their headache history, if any. Of the 102 subjects, 38 were diagnosed as having migraine headaches, 22 had nonmigraine headaches, and 42 were considered to be nonheadache subjects; 82% of those with migraines were stripe sensitive while only 6.2% without migraines were stripe sensitive. We conclude that stripe aversiveness is related to migraine headaches and can assist differentiation of migraine and nonmigraine headaches.     

Local control and function after twice-a-day radiotherapy for Ewing's sarcoma of bone

Between February 1982 and December 1987, 39 patients with Ewing's sarcoma of bone have been treated at the University of Florida with a twice-a-day radiotherapy regimen to their primary lesion, 35 with radiation alone and 4 with a combination of radiation and surgery. Although three separate systemic regimens were used (standard risk, 1982-1987 [SR-1]; high-risk, 1982-1984 [HR-2]; and high-risk, 1985-1987 [HR-3]), the radiotherapy regimen remained constant through the years of the study. Those patients whose soft-tissue mass completely regressed after induction chemotherapy received 5040 cGy (as did patients with no soft-tissue mass at diagnosis), those who had 50% or greater resolution of the soft-tissue mass received 5520 cGy, and those who had less than 50% regression of the soft-tissue mass or progressive disease during induction chemotherapy received 6000 cGy. All patients were treated with 120 cGy twice a day and a 6-hr separation between fractions. Thirteen patients also received 800 cGy of total body radiotherapy (TBI) 1 to 3 months after local radiotherapy as part of their systemic treatment. In the 33 patients treated with radiotherapy alone who were eligible for local control analysis, there have been three local failures to date, all within the first 21 months after diagnosis. The 5-year local control rate was 88% for SR-1, 80% for HR-2, and 92% for HR-3. Local control was not related to total dose, but by design, the patients with the largest lesions and the poorest response to chemotherapy had the highest doses. In the 20 patients presenting with extremity primary lesions, there have been no pathologic fractures. In patients evaluated for limb function, the late effects have been minimal. The twice-a-day regimen used appears to produce good local control rates with improved long-term function as compared with once-a-day regimens.