Older Breast Cancer Survivors: Factors Associated with Self-reported Symptoms of Persistent Lymphedema Over 7 years of Follow-up

Lymphedema of the arm is a common complication of breast cancer with symptoms that can persist over long periods of time. For older women (over 50% of breast cancer cases) it means living with the potential for long-term complications of persistent lymphedema in conjunction with the common diseases and disabilities of aging over survivorship. We identified women > or =65 years diagnosed with primary stage I-IIIA breast cancer. Data were collected over 7 years of follow-up from consenting patients' medical records and telephone interviews. Data collected included self-reported symptoms of persistent lymphedema, breast cancer characteristics, and selected sociodemographic and health-related characteristics. The overall prevalence of symptoms of persistent lymphedema was 36% over 7 years of follow-up. Having stage II or III (OR = 1.77, 95% CI: 1.07-2.93) breast cancer and having a BMI >30 (OR = 3.04, 95% CI: 1.69-5.45) were statistically significantly predictive of symptoms of persistent lymphedema. Women > or =80 years were less likely to report symptoms of persistent lymphedema when compared to younger women (OR = 0.44, 95% CI: 0.18-0.95). Women with symptoms of persistent lymphedema consistently reported worse general mental health and physical function. Symptoms of persistent lymphedema were common in this population of older breast cancer survivors and had a noticeable effect on both physical function and general mental health. Our findings provide evidence of the impact of symptoms of persistent lymphedema on the quality of survivorship of older women. Clinical and research efforts focused on risk factors for symptoms of persistent lymphedema in older breast cancer survivors may lead to preventative and therapeutic measures that help maintain their health and well-being over increasing periods of survivorship.

Swiss warmblood horse with symptoms of hereditary equine regional dermal asthenia without mutation in the cyclophylin B gene (PPIB)

Hereditary equine dermal asthenia (HERDA) is an autosomal recessive skin disease that affects predominantly Quarter Horses and related breeds. Typical symptoms are easy bruising and hyperextensible skin on the back. The prognosis is guarded, as affected horses cannot be ridden normally and are often euthanised. In the Quarter Horse, HERDA is associated with a mutation in cyclophilin B (PPIB), an enzyme involved in triple helix formation of collagen. Here we describe the case of a Swiss Warmblood filly with symptoms of HERDA without PPIB-mutation and in which we also could exclude Ehlers-Danlos syndrome Type IV, VI, VIIA, VIIB and VIIC (dermatosparaxis type) as etiological diseases.

Novel oxazolo-oxazole derivatives of FTY720 reduce endothelial cell permeability, immune cell chemotaxis and symptoms of experimental autoimmune encephalomyelitis in mice

The immunomodulatory FTY720 (fingolimod) is presently approved for the treatment of relapsing-remitting multiple sclerosis. It is a prodrug that acts by modulating sphingosine 1-phosphate (S1P) receptor signaling. In this study, we have developed and characterized two novel oxazolo-oxazole derivatives of FTY720, ST-968 and the oxy analog ST-1071, which require no preceding activating phosphorylation, and proved to be active in intact cells and triggered S1P1 and S1P3, but not S1P2, receptor internalization as a result of receptor activation. Functionally, ST-968 and ST-1071 acted similar to FTY720 to abrogate S1P-triggered chemotaxis of mouse splenocytes, mouse T cells and human U937 cells, and reduced TNFa- and LPS-stimulated endothelial cell permeability. The compounds also reduced TNFα-induced ICAM-1 and VCAM-1 mRNA expression, but restored TNFα-mediated downregulation of PECAM-1 mRNA expression. In an in vivo setting, the application of ST-968 or ST-1071 to mice resulted in a reduction of blood lymphocytes and significantly reduced the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice comparable to FTY720 either by prophylactic or therapeutic treatment. In parallel to the reduced clinical symptoms, infiltration of immune cells in the brain was strongly reduced, and in isolated tissues of brain and spinal cord, the mRNA and protein expressions of ICAM-1 and VCAM-1, as well as of matrix metalloproteinase-9 were reduced by all compounds, whereas PECAM-1 and tissue inhibitor of metalloproteinase TIMP-1 were upregulated. In summary, the data suggest that these novel butterfly derivatives of FTY720 could have considerable implication for future therapies of multiple sclerosis and other autoimmune diseases.

Use of modern and traditional products to self-treat symptoms of sexually transmitted infections in South African women

The objective of the study is to investigate products used by women self-treating symptoms of reproductive tract infections (RTIs), including sexually transmitted infections (STIs), and their methods of administration. A household survey using a multi-stage cluster sample design was undertaken in KwaZulu-Natal, South Africa. Women aged 18-60 years were interviewed (n = 867) and information was collected on demographics, reproductive health and sexual behaviours. A fifth of women reported having RTI/STI symptoms (20.5%), of whom 41.9% were treating these symptoms (mostly discharge [79.1%], ulcers [6.8%] and itching [7.7%]). Only three women were using medication prescribed by a health provider, while the remainder were self-treating using traditional medicines and modern products, including antiseptics, soaps, petroleum jelly, menthol creams and alum. Products were administered in various ways. Although RTI/STI treatment is widely available and free in public health facilities, many women are still self-treating. Potential harm of products for self-treatment requires further investigation and efforts should be made to improve STI service uptake.

Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke

Glial fibrillary acidic protein (GFAP) is a biomarker candidate indicative of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. GFAP is released rapidly in the presence of expanding intracerebral bleeding, whereas a more gradual release occurs in ischemic stroke. In this study the diagnostic accuracy of plasma GFAP was determined in a prospective multicenter approach.

Deep brain stimulation of the globus pallidus internal improves symptoms of chorea-acanthocytosis

Chorea-acanthocytosis is a rare autosomal recessive disorder. To date, treatment is only symptomatic and supportive. Results from the few reports of chorea-acanthocytosis patients treated with deep brain stimulation (DBS) have been inconsistent. We present case reports for two patients with chorea-acanthocytosis who received DBS treatment and compare the outcomes with results from the literature. Both patients showed the typical clinical features of chorea-acanthocytosis with motor symptoms resistant to medical treatment. Chorea was significantly improved following low-frequency DBS treatment in both patients. However, dystonia was only mildly improved. Four chorea-acanthocytosis patients treated with DBS treatment have been reported in the literature. One patient had improvement with low-frequency DBS stimulation, while another two had improvement with higher-frequency DBS. One patient, however, did not improve with either low-frequency or high-frequency DBS. Bilateral DBS to the GPi can improve chorea and dystonia in some patients with intractable chorea-acanthocytosis. However, selection criteria for the most promising candidates must be defined, and the long-term benefits evaluated in clinical studies.

NADPH P450 oxidoreductase: structure, function, and pathology of diseases

Cytochrome P450 oxidoreductase (POR) is an enzyme that is essential for multiple metabolic processes, chiefly among them are reactions catalyzed by cytochrome P450 proteins for metabolism of steroid hormones, drugs and xenobiotics. Mutations in POR cause a complex set of disorders that often resemble defects in steroid metabolizing enzymes 17α-hydroxylase, 21-hydroxylase and aromatase. Since our initial reports of POR mutations in 2004, more than 200 different mutations and polymorphisms in POR gene have been identified. Several missense variations in POR have been tested for their effect on activities of multiple steroid and drug metabolizing P450 proteins. Mutations in POR may have variable effects on different P450 partner proteins depending on the location of the mutation. The POR mutations that disrupt the binding of co-factors have negative impact on all partner proteins, while mutations causing subtle structural changes may lead to altered interaction with specific partner proteins and the overall effect may be different for each partner. This review summarizes the recent discoveries related to mutations and polymorphisms in POR and discusses these mutations in the context of historical developments in the discovery and characterization of POR as an electron transfer protein. The review is focused on the structural, enzymatic and clinical implications of the mutations linked to newly identified disorders in humans, now categorized as POR deficiency.

Etiology and symptoms of severe hypokalemia in emergency department patients

To investigate the prevalence, etiology, and symptoms of severe hypokalemia in patients presenting to the emergency department.

Radiofrequency electromagnetic field exposure and non-specific symptoms of ill health: A systematic review

This article is a systematic review of whether everyday exposure to radiofrequency electromagnetic field (RF-EMF) causes symptoms, and whether some individuals are able to detect low-level RF-EMF (below the ICNIRP [International Commission on Non-Ionizing Radiation Protection] guidelines). Peer-reviewed articles published before August 2007 were identified by means of a systematic literature search. Meta-analytic techniques were used to pool the results from studies investigating the ability to discriminate active from sham RF-EMF exposure. RF-EMF discrimination was investigated in seven studies including a total of 182 self-declared electromagnetic hypersensitive (EHS) individuals and 332 non-EHS individuals. The pooled correct field detection rate was 4.2% better than expected by chance (95% CI: -2.1 to 10.5). There was no evidence that EHS individuals could detect presence or absence of RF-EMF better than other persons. There was little evidence that short-term exposure to a mobile phone or base station causes symptoms based on the results of eight randomized trials investigating 194 EHS and 346 non-EHS individuals in a laboratory. Some of the trials provided evidence for the occurrence of nocebo effects. In population based studies an association between symptoms and exposure to RF-EMF in the everyday environment was repeatedly observed. This review showed that the large majority of individuals who claims to be able to detect low level RF-EMF are not able to do so under double-blind conditions. If such individuals exist, they represent a small minority and have not been identified yet. The available observational studies do not allow differentiating between biophysical from EMF and nocebo effects.

Loss of pulp sensitivity and pain as the first symptoms of a Ewing's sarcoma in the right maxillary sinus and alveolar process: report of a case

This case report describes the diagnosis and treatment of a Ewing's sarcoma in the right maxillary sinus and alveolar bone of a 19-year-old female patient. The first clinical symptoms were a loss of sensitivity of the premolars and first molar in the right maxilla and acute pain located in the area of these teeth. Initially, the referring dentist had treated these findings as an acute apical periodontitis with root canal medication. Because swellings on the palatal and buccal aspects of the teeth occurred and could not be treated with incision and drainage, the dentist referred the patient. Cone-beam computed tomography revealed a proliferation of soft tissue in the right maxillary sinus, with a radiopaque material at the tip of the mesiobuccal root of the first molar and resorptive signs of the mesiobuccal and distobuccal roots of the first molar. The palatal cortical bone of the right alveolar process seemed to be intact. After explorative surgery with biopsies from the buccal, palatal, and sinus proliferation areas, the pathologist diagnosed the lesion as a Ewing's sarcoma. Treatment of the patient consisted of initial chemotherapy, hemimaxillectomy, and postsurgical chemoradiotherapy.

Correlation between symptoms of pain and peritoneal fluid inflammatory cytokine concentrations in endometriosis

Endometriosis affects 10-20% of women during reproductive age and is a common cause of infertility and pain leading to work absenteeism and reduced quality of life.The objective of this study was to investigate the association between the presence and concentration of interleukin-8 (IL-8), RANTES, osteoprotegerin (OPG), pregnancy-associated plasma protein A (PAPP-A), tumour necrosis factor-alpha (TNF-alpha), midkine and glycodelin in the peritoneal fluid (PF) and the intensity of pain reported by patients undergoing laparoscopy in our clinic. They rated their pain during menstruation, intercourse and lower abdominal using a visual analogue scale. During laparoscopy, PF was aspirated. Pain scores were correlated to the concentration of the above substances in the PF and to the stage of endometriosis. Endometriosis was histologically confirmed in 41 of 68 participating women; 27 without such evidence were considered as controls. TNF-alpha and glycodelin correlated positively with the level of menstrual pain. For IL-8, RANTES, OPG and PAPP-A no correlation between their PF concentration and the menstrual pain scores was observed. Patients with severe dysmenorrhoea had increased PF cytokine and marker levels; the difference was significant for TNF-alpha and glycodelin when compared with the other patients (no or moderate pain). TNF-alpha and glycodelin may thus play a role in endometriosis and the severity of menstrual pain.

Symptoms of endocrine treatment and outcome in the BIG 1-98 study

There may be a relationship between the incidence of vasomotor and arthralgia/myalgia symptoms and treatment outcomes for postmenopausal breast cancer patients with endocrine-responsive disease who received adjuvant letrozole or tamoxifen. Data on patients randomized into the monotherapy arms of the BIG 1-98 clinical trial who did not have either vasomotor or arthralgia/myalgia/carpal tunnel (AMC) symptoms reported at baseline, started protocol treatment and were alive and disease-free at the 3-month landmark (n = 4,798) and at the 12-month landmark (n = 4,682) were used for this report. Cohorts of patients with vasomotor symptoms, AMC symptoms, neither, or both were defined at both 3 and 12 months from randomization. Landmark analyses were performed for disease-free survival (DFS) and for breast cancer free interval (BCFI), using regression analysis to estimate hazard ratios (HR) and 95 % confidence intervals (CI). Median follow-up was 7.0 years. Reporting of AMC symptoms was associated with better outcome for both the 3- and 12-month landmark analyses [e.g., 12-month landmark, HR (95 % CI) for DFS = 0.65 (0.49–0.87), and for BCFI = 0.70 (0.49–0.99)]. By contrast, reporting of vasomotor symptoms was less clearly associated with DFS [12-month DFS HR (95 % CI) = 0.82 (0.70–0.96)] and BCFI (12-month DFS HR (95 % CI) = 0.97 (0.80–1.18). Interaction tests indicated no effect of treatment group on associations between symptoms and outcomes. While reporting of AMC symptoms was clearly associated with better DFS and BCFI, the association between vasomotor symptoms and outcome was less clear, especially with respect to breast cancer-related events.