Psychological adjustment to familial-genetic risk assessment for ovarian cancer: predictors of nonadherence to surveillance recommendations.

OBJECTIVE: To evaluate whether self-report measures of psychological distress and perceived risk were associated with nonadherence to recommended ovarian cancer surveillance. METHODS: Eighty-three patients attending the Familial Ovarian Cancer Clinic (FOCC) at Princess Margaret Hospital were assessed psychosocially prior to and during initial familial-genetic assessment and then monitored for adherence with recommended follow-up surveillance over a period of 12-18 months. The assessment protocol included an investigator-designed clinic questionnaire, the State-Trait Anxiety Inventory (STAI), Center for Epidemiologic Studies Depression Scale (CESD), Life Orientation Test (LOT), Medical Outcomes Study Social Support Survey (MOSSS), Texas Inventory of Grief, and the COPE. Nonadherence was measured in terms of unexplained absences at one or two recommended and scheduled surveillance appointments following the familial-genetic assessment. RESULTS: Univariate tests revealed a significant association between higher perception of ovarian cancer risk, as assessed immediately after the familial-genetic risk assessment in the clinic and nonadherence to physician-recommended surveillance (chi2 (2, N = 83) = 9.75, P < 0.008). Empirically based estimates of risk, conveyed by the clinic team to subjects, were not significantly associated with nonadherence (chi2 (2, N = 83) = 0.19, P = 0.91). Logistic regression analysis revealed that subjects who perceived themselves to be at high ovarian cancer risk were five times more likely to be nonadherent than participants who perceived themselves to be at low or medium ovarian cancer risk. CONCLUSIONS: These results suggest that higher self-perceived risk may predict adherence difficulties to recommended surveillance in women attending a familial-genetic risk clinic.     

Effects of a new clinically relevant antiestrogen (GW5638) related to tamoxifen on breast and endometrial cancer growth in vivo.

PURPOSE: Cross-resistance is an important issue for the evaluation of new antiestrogens to treat advanced breast cancer patients who have failed tamoxifen therapy. In addition, postmenopausal patients treated with long-term adjuvant tamoxifen show a 3-4-fold increase in the risk of developing endometrial cancer. Consequently, a new second line agent should be more antiestrogenic and less estrogen-like on the uterus, and be effective at controlling the growth of breast cancer after exposure to tamoxifen. The purpose was to evaluate the effects of the new tamoxifen analogue GW5638 on breast and endometrial cancer growth. EXPERIMENTAL DESIGN: Athymic mice were transplanted with an endometrial tumor model (ECC-1 E2) that is responsive to estrogen and has never been exposed to antiestrogen. In addition, we used three breast tumor models: a tamoxifen-na?ve tumor (T47D-E2) and two tamoxifen-stimulated tumors (MT2 TAM and MCF-7 TAM LT). The antiestrogen GW5638 (1.5 mg daily), tamoxifen (0.5 mg or 1.5 mg daily), and raloxifene (1.5 mg daily) were given p.o. The pure antiestrogen ICI182,780 (5 mg once a week) was given s.c. Western blots from MCF-7 TAM breast tumors were performed to demonstrate the regulation of estrogen receptor alpha expression by different ligands. RESULTS: Estradiol and GW5638 down-regulated the receptor compared with control. ICI182,780 completely degraded the receptor but tamoxifen had no effect. GW5638 did not promote tumor growth, and was effective in blocking the effects of postmenopausal estradiol on the growth of tamoxifen-na?ve breast and endometrial tumors. However, raloxifene did not completely block the effects of postmenopausal estradiol on the growth of tamoxifen-na?ve endometrial tumor after 14 weeks. GW5638 and ICI182,780 but not raloxifene were also effective in blocking the tamoxifen-stimulated breast tumor growth in athymic mice. CONCLUSIONS: GW5638 is more effective than raloxifene in blocking the effect of estrogen on tamoxifen-na?ve endometrial cancer. More importantly, GW5638, like the pure antiestrogen ICI182,780, is able to block the growth of breast cancer stimulated by tamoxifen differently from raloxifene. GW5638 down-regulates estrogen receptor but does not completely destroy the receptor. Therefore, based on our findings, GW5638 could be developed as a second line agent for advanced breast cancer patients and an important first line agent to evaluate as an adjuvant treatment or chemopreventive.     

Assessment of the risk/benefit ratio of phase II cancer clinical trials by Institutional Review Board (IRB) members.

BACKGROUND: This study examined the assessment of risk/benefit ratios for phase II cancer clinical trials by Institutional Review Board (IRB) members. PATIENTS AND METHODS: Semi-structured interviews were conducted with 53 IRB members from six research hospitals and specialized cancer centers in The Netherlands. RESULTS: While the toxicity and side-effects of treatment were most often identified as risks associated with participating in a phase II trial, approximately two-thirds of IRB members also cited psychosocial and/or quality-of-life risks. Conversely, 68% of the respondents identified psychosocial benefits of trial participation, while 25% cited treatment effectiveness as a possible benefit. Between one-quarter and two-thirds of respondents indicated that trial protocols provide insufficient information regarding the likelihood, magnitude and duration of both risks and benefits. Between 15% and 34% of IRB members reported feeling less than fully competent at evaluating various aspects of phase II protocols (e.g. originality and feasibility of the study, adequacy of the methods and analysis procedures, etc.). This was particularly the case for non-physician IRB members. Few IRB members reported weighing risks and benefits in a systematic manner, but rather relied on global impressions or preferred to leave such matters to the IRB as a whole or to their patients. CONCLUSIONS: A substantial minority of IRB members believes that trial protocols provide too little information relevant to evaluating various cost/benefit and scientific issues, and feels less than fully competent in carrying out such evaluations. IRB members are more likely to identify psychosocial benefits than physical health benefits that may accrue to patients participating in phase II trials.     

Promising hypotensive effect of hawthorn extract: a randomized double-blind pilot study of mild, essential hypertension.

This pilot study was aimed at investigating the hypotensive potential of hawthorn extract and magnesium dietary supplements individually and in combination, compared with a placebo. Thirty-six mildly hypertensive subjects completed the study. At baseline, anthropometric and dietary assessment, as well as blood pressure measurements were taken at rest, after exercise and after a computer 'stress' test. Volunteers were then randomly assigned to a daily supplement for 10 weeks of either: (a) 600 mg Mg, (b) 500 mg hawthorn extract, (c) a combination of (a) and (b), (d) placebo. Measurements were repeated at 5 and 10 weeks of intervention. There was a decline in both systolic and diastolic blood pressure in all treatment groups, including placebo, but ANOVA provided no evidence of difference between treatments. However, factorial contrast analysis in ANOVA showed a promising reduction (p = 0.081) in the resting diastolic blood pressure at week 10 in the 19 subjects who were assigned to the hawthorn extract, compared with the other groups. Furthermore, a trend towards a reduction in anxiety (p = 0.094) was also observed in those taking hawthorn compared with the other groups. These findings warrant further study, particularly in view of the low dose of hawthorn extract used.     

Landau-Kleffner syndrome: course and correlates with outcome

The presenting characteristics of 18 (11 female, seven male) children with Landau-Kleffner syndrome (LKS) were studied with respect to course and outcome of their condition at a mean length of 67 (SD 46) months' follow-up. All had regression of receptive language (mean age of onset 4 years 9 months) and electrical status epilepticus in sleep (ESES). Length of ESES correlated strongly with length of period between onset of illness and onset of recovery (p<0.006) and also with eventual receptive (p<0.001) and expressive (p<0.007) language. Behaviour during the acute phase was severely affected in nine children and associated with frontal lobe discharges in awake EEGs (p<0.004). Age at onset was not correlated with outcome. All children had impaired short-term memory at follow-up. Three children had language outcome within the normal range. No child with ESES lasting longer than 36 months had normal language outcome. These data lend support for intervention in ending ESES by 36 months using multiple subpial transection (MST) if steroids are ineffective or cause unacceptable side effects.     

Multiple subpial transection in Landau-Kleffner syndrome

We have considered multiple subpial transection (MST) as a treatment option for Landau-Kleffner syndrome (LKS) for the past 6 years. The effect of this technique on language and cognitive ability, behaviour, seizures, and EEG abnormalities is analysed here. Five children (4 males, 1 female; aged 5.5 to 10 years) underwent MST with sufficiently detailed pre- and postoperative data for analysis. Behaviour and seizure frequency improved dramatically after surgery in all children. Improvement in language also occurred in all children, although none improved to an age-appropriate level. All five had electrical status epilepticus in sleep (ESES) before surgery, which was eliminated by the procedure. One child has had an extension of his MST due to the recurrence of ESES and accompanying clinical deterioration with good effect. An attempt is made to set the effect of MST against the natural history of the condition. MST is an important treatment modality in LKS, although the timing of this intervention and its effect on final language outcome remains to be defined.     

Synovial osteochondromatosis complicating pilon fracture of the tibia

A case of previously undiagnosed synovial osteochondromatosis complicating a tibial pilon fracture is presented. The entrapment of osteochondral bodies within the fracture margin prevented complete reduction of the fracture and necessitated surgical intervention. Received: 27 December 2000 Revision requested: 26 January 2001 Revision received: 19 March 2001 Accepted: 21 March 2001     

Deriving the indications for laparoscopic appendectomy from a comparison of the outcomes of laparoscopic and open appendectomy

BACKGROUND: Indications for laparoscopic appendectomy (LA) remain controversial and poorly defined. We sought to identify indications for LA through a comparison of LA and open appendectomies (OA). METHODS: We reviewed demographics, coexisting medical conditions, radiology and pathology data, hospital course, and complications from charts on all LA patients and a comparison group of OA done from 1991 to 1998. RESULTS: The following were significantly associated with LA: female sex, higher mean body mass index (BMI), coexisting medical problems, private insurance, and daytime surgery. The OA group was significantly more likely to have: a radiology report suggesting the diagnosis of acute appendicitis, perforation of the appendix, intensive care unit admission, and complications in their hospital course. Forty-one percent of the LA patients did not have appendicitis, compared with 20% of the OA patients. CONCLUSIONS: Daytime surgery, women, private insurance, coexisting medical problems, prior abdominal surgery, higher BMI, and less severe disease appear to be used by surgeons as indicators for LA. The threshold for surgical exploration appears to be lower for LA.     

Near-infrared spectroscopy versus compartment pressure for the diagnosis of lower extremity compartmental syndrome using electromyography-determined measurements of neuromuscular function

BACKGROUND: Compartmental syndrome (CS) is difficult to diagnose in intensive care unit patients. Compartment perfusion pressure (CPP) is an invasive, indirect measure of ischemia. Near-infrared spectroscopy is noninvasive, and directly measures ischemia by transmitting light through tissues at wavelengths that react with hemoglobin to provide percent tissue oxygen saturation (Sto(2)). Animal studies demonstrate that Sto(2) is superior to CPP for detecting CS. However, there are no studies in humans comparing Sto(2) with CPP. We hypothesized that Sto(2) can reliably detect CS, and is superior to CPP. METHODS: CS was induced in 15 human volunteers using a standard calf compression model. At 30-minute intervals, compression was increased to reduce Sto(2) from baseline (86% +/- 4%) to 60%, 40%, 20%, and < 10%, with simultaneous recording of CPP. Outcome variables included deep peroneal nerve conduction assessed by electromyography, cutaneous peroneal nerve sensitivity using Semmes-Weinstein monofilaments, and pain (visual analog scale). RESULTS: Both Sto(2) and CPP significantly correlated with all ischemia outcome variables (p < 0.001). Receiver operating characteristic curves of deep peroneal nerve conduction demonstrated that Sto(2) had higher sensitivity than CPP for detecting > 50% block. For example, when specificity was 83% for Sto(2) and 84% for CPP, sensitivity was 85% versus 56%, respectively (p = 0.02). When specificity for both was 72%, sensitivity was 94% for Sto(2) versus 76% for CPP (p = 0.04). CONCLUSION: In intensive care unit patients who cannot alert physicians to symptoms, near-infrared spectroscopy may help clinicians to avoid delayed or unnecessary prophylactic fasciotomy, and provides the benefits of a continuous, noninvasive monitoring technique.