Giant abdominopelvic epithelioid angiomyolipoma associated with tuberous sclerosis: Report of a case

(Received for publication on July 16, 1998; accepted on Mar. 11, 1999)     

Compliance with consensus recommendations for systemic therapy is associated with improved survival of women with node-negative breast cancer.

PURPOSE: The impact of consensus recommendations for systemic therapy on outcome of disease is unclear. We evaluated if compliance with guidelines for systemic adjuvant treatment is associated with improved survival of women with node-negative breast cancer. PATIENTS AND METHODS: The study population included women diagnosed with invasive node-negative breast cancer in Québec, Canada, in 1988 to 1989, 1991 to 1992, and 1993 to 1994. Information was collected by chart review, linkage with administrative databases, and queries to attending physicians. Guidelines from the 1992 St Gallen conference were used as standard of care. Survival was estimated by Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Among 1,541 women, 358 died before December 1999. Median follow-up was 6.8 years. Seven-year event-free and overall survivals were 66% and 81%, respectively. Survival was 88%, 84%, and 74% in women at minimal, moderate, or high risk of recurrence. Virtually all women at minimal risk were treated according to the consensus (98.4% of 370). In comparison, adjusted hazard ratios of death were 1.0 (95% CI, 0.6 to 1.7) and 2.3 (95% CI, 1.3 to 4.0) among women at moderate risk treated according to the consensus or not, respectively. Among women at high risk, adjusted hazard ratios of death were 2.0 (95% CI, 1.4 to 2.8) and 2.7 (95% CI, 1.9 to 3.9), respectively. Both risk category (P <.0005) and compliance with guidelines (P <.0005) were independent significant predictors of survival. CONCLUSION: Treatment according to consensus recommendations is associated with improved survival of women with breast cancer in the community. Promoting the adoption of guidelines for treatment is an effective strategy for disease control.     

Cyclooxygenase-2 activation mediates the proangiogenic effect of nitric oxide in colorectal cancer.

PURPOSE: Up-regulation of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes has been reported in colorectal cancer. We aimed at evaluating the possible interaction between the nitric oxide and COX-2 pathways, and its effect on promoting tumor angiogenesis. EXPERIMENTAL DESIGN: Expression of iNOS, COX-2, vascular endothelial growth factor (VEGF), and CD31 was analyzed in tumor samples and corresponding normal mucosa obtained from 46 surgical specimens. We also evaluated iNOS activity, prostaglandin E(2) (PGE(2)), cyclic GMP and cyclic AMP production in the same specimens. Nitrite/nitrate levels, and PGE(2) and VEGF production were assessed in HCT116 and HT29 colon cancer cell lines after induction and selective inhibition of the two enzyme pathways. RESULTS: A significant correlation was found between iNOS and COX-2 immunohistochemical expression. PGE(2) production significantly correlated with iNOS activity and cGMP levels. A significant correlation was also found among PGE(2) production, microvessel density, and VEGF expression. Coinduction of both iNOS and COX-2 activities occurred after lipopolysaccharide (LPS) and epidermal growth factor (EGF) treatment in HCT116 and HT29 cells. Inhibition of iNOS by 1400W significantly reduced both LPS- and EGF-induced PGE(2) production. Treatment with LPS, EGF, and arachidonic acid significantly increased VEGF production in the iNOS-negative/COX-2-positive HT29 cells. This effect was completely reversed by treatment with the selective COX-2 inhibitor celecoxib. CONCLUSIONS: Our data showed a prominent role of nitric oxide in stimulating COX-2 activity in colorectal cancer. This interaction is likely to produce a cooperative effect in promoting angiogenesis through PGE(2)-mediated increase in VEGF production.     

Abnormalities of the soleus H-reflex in lumbar spondylolisthesis: a possible early sign of bilateral S1 root dysfunction

Using routine electrodiagnostic procedures, the authors searched for physiologic evidence of nerve root compromise in patients with chronic mechanical perturbation to the lumbar spine. They examined 37 patients with spondylolisthesis and various degrees of degenerative changes in the lumbar canal. Clinical and neurophysiologic findings were compared with data obtained from 36 healthy persons. The soleus H-reflex appeared to be a sensitive indicator of sensory fiber compromise at the S1 root level, because changes correlated well with the focal sensory signs and preceded clinical and electromyographic signs of motor root involvement. When these occurred, the clinical findings were consistent with a more severe nerve root deficit and with radiographic evidence of neural compression. The greater sensitivity of the soleus H-reflex may be related to the pathophysiologic events that occur at the lesion site.     

Detection and clinical implications of early systemic tumor cell dissemination in breast cancer.

Blood-borne distant metastasis is the leading cause of cancer-related death in breast cancer. The onset of this fundamental process can now be assessed in cancer patients using ultrasensitive immunocytochemical and molecular assays able to detect even single metastatic cells. Analyses of bone marrow (BM) samples show that disseminated cells are present in 20-40% of primary breast cancer patients without any clinical or histopathological signs of metastasis. The common homing of circulating breast cancer cells in BM is indicative for systemic tumor cell spread and predictive for growth of overt metastases in relevant organ sites such as bone, lung, or liver. Recent clinical studies involving more than 3000 breast cancer patients demonstrated that the presence of tumor cells in BM at primary diagnosis is an independent prognostic factor for unfavorable clinical outcome. To date, sampling of BM, however, is not a routine procedure in clinical management of breast cancer patients. Therefore, several research groups have developed sensitive assays for detection of circulating tumor cells in peripheral blood. Studies evaluating the clinical relevance of these blood assays are ongoing. Here, we will review the existing tumor cell assays and discuss their current clinical relevance and perspectives for the clinical management of breast cancer patients.     

Quality of life in tuberculosis: Patient and provider perspectives

Tuberculosis (TB) is a persistent problem in the United States; however, little is known about its impact on functioning and quality of life (QOL) among people with TB. The purpose of this study is to describe the impact of TB on patients' QOL by using focus groups to assess the domains of QOL that are affected. Participants included patients (n = 10) who received treatment for active TB and physicians (n = 4) and nurses (n = 9) caring for patients with TB at a public health clinic in Baltimore, Maryland. TB affected all predicted domains of QOL, including general health perceptions, somatic sensation, psychological health, spiritual well-being, and physical, social and role functioning. Social stigmatization, isolation, pill burden, long duration of therapy, sexual dysfunction, loss of income, and fear were additional specific problems related to TB. Surprisingly, 11% (33) of the comments described benefits of TB illness, including increased spirituality and improved life perspectives. In addition, four additional QOL domains and three elements of treatment specific to TB which substantially impact QOL were identified. While patients and clinicians both identified issues in many areas of QOL, only patients mentioned the impact on sexual function, spirituality and improved life perspectives. Despite available curative therapy, TB and its treatment still have significant short and long-term consequences on patients' QOL.     

Epidemiology of Travelers— Diarrhea: Details of a Global Survey

Background Recent epidemiologic data on travelers— diarrhea (TD) are essential for the evaluation of conventional and future prophylactic and therapeutic measures.
Methods To determine the epidemiology, including risk factors, impact and quality-of-life evaluation of TD, a cross-sectional survey was conducted over 12 months at the airports of Mombasa (Kenya), Goa (India), Montego Bay (Jamaica) and Fortaleza (Brazil) by distributing questionnaires to visitors just prior to their flying home. The study period was March 1996 to July 1998.
Results Overall, 73,630 short-term visitors completed a questionnaire. The total diarrhea attack rate varied between a high of 54.6% in Mombasa and a low of 13.6% in Fortaleza, but only between 31.5% and 5.4% of all travelers had classic TD. The 14-day incidence rates varied between 19.5% and 65.7%. Few travelers meticulously avoided potentially dangerous food items, although in India and Kenya most travelers avoided those considered most dangerous. Risk factors were stays exceeding 1 week, age between 15 and 30 years, and residence in the UK. The impact, measured as incapacity or quality-of-life scores, was very considerable.
Conclusions TD continues to affect vacationers and business travelers as frequently as it did some 20 years ago. Compliance with recommendations to reduce exposure to pathogens by avoiding dangerous food items is poor among travelers from all countries. Implementation of food safety education programs may be difficult to achieve.     

Influence of intensive lipid‐lowering on CT derived fractional flow reserve in patients with stable chest pain: Rationale and design of the FLOWPROMOTE study

IntroductionCoronary CT angiography (CTA) derived fractional flow reserve (FFR_CT) shows high diagnostic performance when compared to invasively measured FFR. Presence and extent of low attenuation plaque density have been shown to be associated with abnormal physiology by measured FFR. Moreover, it is well established that statin therapy reduces the rate of plaque progression and results in morphology alterations underlying atherosclerosis. However, the interplay between lipid lowering treatment, plaque regression, and the coronary physiology has not previously been investigated.AimTo test whether lipid lowering therapy is associated with significant improvement in FFR_CT, and whether there is a dose–response relationship between lipid lowering intensity, plaque regression, and coronary flow recovery.MethodsInvestigator driven, prospective, multicenter, randomized study of patients with stable angina, coronary stenosis ≥50% determined by clinically indicated first‐line CTA, and FFR_CT ≤ 0.80 in whom coronary revascularization was deferred. Patients are randomized to standard (atorvastatin 40 mg daily) or intensive (rosuvastatin 40 mg + ezetimibe 10 mg daily) lipid lowering therapy for 18 months. Coronary CTA scans with blinded coronary plaque and FFR_CT analyses will be repeated after 9 and 18 months. The primary endpoint is the 18‐month difference in FFR_CT using (1) the FFR_CT value 2 cm distal to stenosis and (2) the lowest distal value in the vessel of interest. A total of 104 patients will be included in the study.ConclusionThe results of this study will provide novel insights into the interplay between lipid lowering, and the pathophysiology in coronary artery disease.     

The clinical course of interstitial lung disease in an adult patient with an ABCA3 homozygous complex allele under hydroxychloroquine and a review of the literature

Objective: The gene mutations responsible for ABCA3 protein deficiency are involved in respiratory distress of the newborn and much more rarely in adult interstitial lung diseases (ILD). An adult patient homozygous for a complex allele encompassing the p.Ala1027Pro likely pathogenic mutation and the p.Gly974Asp variation was followed for a late-onset and fibrotic ILD. The evolution was marked by progressive clinical and functional degradation despite corticosteroid pulses. The patient, who was first registered on the list for lung transplantation, was improved quickly and persistently for at least 6.5 years with hydroxychloroquine treatment, allowing removal from the transplant list.     

Psychometric properties of the Copenhagen Burnout Inventory (CBI) in Italian Physicians

Background:This study aimed to standardize the Copenhagen Burnout Inventory (CBI), a psychometrically sound, worldwide-spread tool among Italian physicians.Methods:Nine hundred and fifteen Italian physicians were web-administered the CBI, Patient Health Questionnaire-8 (PHQ-8), Generalized Anxiety Disorder-7 (GAD-7) and General Self-Efficacy Scale (GSE). The present CBI included 18 items (range=19-90) assessing Personal, Work-related and Client-related Burnout. Client-related adaptation was performed. Construct validity, factorial structure (Confirmatory Factor Analysis) and internal consistency were tested. Diagnostic accuracy was assessed simultaneously against the PHQ-8, GAD-7 and GSE. All CBI measures yielded optimal internal consistency (Cronbach’s α=0.90-0.96).Results:The CBI met its original three-factor model (CFI=0.94; TLI=0.93; RMSEA=0.09; SRMR=0.04), was positively related to the PHQ-8 (r=0.76) and GAD-7 (r=0.73), whereas negatively with the GSE (r=0.39) and yielded optimal diagnostics (AUC=0.93; sensitivity=0.91 and specificity=0.85 at the optimal cutoff of 69/90).Conclusion:The CBI is thus a valid, reliable, and normed tool to assess burnout levels in physicians.