Childhood intermittent exotropia from a different angle: does severity affect quality of life?

BACKGROUND: Few studies have explored the relationship between health-related quality of life (HRQOL) and clinical severity of childhood intermittent exotropia (IXT) measured by angle of deviation, control and stereoacuity. METHODS: Sixty-eight consecutive children aged 5-17 years with childhood IXT who attended the paediatric eye clinic were recruited. One accompanying parent was recruited concurrently. Child, parent and proxy (parent about the child) HRQOL was measured using the IXT questionnaire (IXTQ). Angle of deviation, control and stereoacuity of the children were measured and correlated with IXTQ scores using Spearman's correlation coefficient and paired t test for differences in child and proxy IXTQ mean scores. RESULTS: The mean age of the children was 9.0±2.6 years. Child HRQOL was not correlated to any strabismus measurements. Poorer parent HRQOL was correlated with poorer distance control (surgery subscale, r=-0.24 p=0.049), poorer near control (surgery subscale, r=-0.30, p=0.013), poorer office near control (mean, r=-0.24, p=0.047; psychological subscale, r=-0.27, p=0.025; surgery subscale, r=-0.28, p=0.020) and larger angle of deviation (psychological subscale, r=-0.30, p=0.013). Poorer proxy HRQOL was correlated with poorer home control (r=-0.28, p=0.022) and larger angle of deviation (r=0.33, p=0.0061). CONCLUSIONS: It is difficult to predict child HRQOL based on clinical measurements. However, parent HRQOL tends to be worse with poorer control and larger angle of deviation. Perhaps HRQOL should be routinely assessed in clinic alongside clinical measurements in order to tailor management appropriately.

Serum tumour necrosis factor-alpha is associated with poor health-related quality of life and depressive symptoms in patients with systemic lupus erythematosus.

OBJECTIVES: While patients with systemic lupus erythematosus (SLE) have poorer health-related quality of life (HRQoL) and are more depressed than healthy people, the impact of proinflammatory cytokines, particularly tumour necrosis factor-alpha (TNFα), on these unfavourable psychosocial parameters is unclear. We aim to explore potential relationships between lupus-related proinflammatory cytokines, HRQoL and depressive symptoms in patients with SLE. METHODS: Patients with SLE and age-matched healthy subjects were assessed for HRQoL and depressive and anxiety symptoms by the Short Form Health Survey-36 (SF-36) and Hospital Anxiety and Depression Scale (HADS) respectively. Using multiplex immunoassay, a panel of serum proinflammatory cytokines including TNFα, interleukin (IL)-1ß, IL-6, IL-17, IL-23 and IL-33 were determined and compared between both groups. Independent associations between SF-36, serum proinflammatory cytokine levels and HADS scores were studied by regression models. RESULTS: In total, 54 patients and 54 healthy controls were studied. Lupus patients had significantly poorer HRQoL (p < 0.001) and were significantly more depressed (p = 0.006) and anxious (p = 0.022) than their healthy counterparts. Amongst the proinflammatory cytokines studied, serum TNFα was significantly higher in lupus patients (p < 0.001). After multivariate adjustment, higher serum TNFα (ß = -0.224, p = 0.047) remained significantly associated with lower SF-36, along with smoking (ß = -0.253, p = 0.014) and more severe depressive symptoms (ß = -0.433, p = 0.002). In healthy subjects, serum TNFα was associated with depressive symptoms but not with SF-36. CONCLUSIONS: Higher serum TNFα level is independently associated with poorer HRQoL and more severe depressive symptoms in SLE patients. These associations suggest a potential impact of inflammatory response on depressive symptoms and the quality of life in patients with SLE.

Lumbar spine bone mineral density predicts endothelial reactivity in patients with systemic lupus erythematosus.

OBJECTIVES: To explore whether endothelial function is related to bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive adult SLE patients and age-, sex-, BMI- and smoking-status-matched healthy controls were studied. Subjects with hypertension, hyperlipidemia, diabetes mellitus, renal impairment, dysthyroidism, history of or treatment for cardiovascular and cerebrovascular disorders, antiphospholipid syndrome, positive antiphospholipid antibodies or bone loss were excluded. Endothelial function was assessed by measuring flow-mediated dilatation (FMD) at the brachial artery and carotid intima-media thickness (IMT) by ultrasound. Lumbar and hip BMD were measured by dual-energy x-ray absorptiometry. Fasting blood samples were assayed for atherogenic index and high sensitivity C-reactive protein (hsCRP). Regression models were constructed to study the relationship between FMD and BMD. RESULTS: One hundred and ten subjects (55 SLE and 55 matched healthy controls) were studied. While there were no differences between SLE patients and controls in menopausal status, blood pressure, atherogenic index, carotid IMT and BMD, SLE patients had significantly poorer FMD even after adjustment for age, gender, smoking and baseline brachial artery diameter. Also, SLE patients with lumbar osteopenia had significantly lower FMD than those with normal BMD. Multivariate regression revealed that lower FMD was associated with lower lumbar BMD and higher serum hsCRP in SLE patients, but these relationships were absent amongst healthy controls. CONCLUSIONS: Lumbar vertebral BMD predicted endothelial reactivity in SLE patients without clinically-overt bone loss and atherosclerosis. Thus, early atherosclerotic disease should be considered in lupus patients especially if vertebral bone loss is evident.

Atherogenic serum lipid profile is an independent predictor for gouty flares in patients with gouty arthropathy.

OBJECTIVE: Atherogenic serum lipid profile possesses pro-inflammatory properties and is associated with more active RA. While prevalent in patients with gout, whether atherogenic lipid profile is associated with gouty flares is unknown. This study aims to investigate whether atherogenic serum lipid predicts gouty flares in patients with gout. METHODS: Adult patients (age > or =21 yrs) who suffered from gout were prospectively followed between September 2006 and November 2007 and their demographic, clinical and laboratory data were collected. Episodes of gouty flares over this observation period were recorded and factors predictive of gouty flares were studied by regression models. RESULTS: Of the 100 patients, 80 were men, 65 were ethnic Chinese, 31 were Malay and the rest were Indian and Caucasian. The mean age and duration of gout (+/-S.D.) were 61.9 +/- 14.0 and 6.6 +/- 7.8 yrs, respectively. The mean serum uric acid and creatinine levels were 537.6 +/- 142.8 and 173.6 +/- 119.9 micromol/l, respectively. In univariate analysis, longer duration of gout, higher adjusted mean serum creatinine, lower adjusted mean fasting serum, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels were associated with gouty flares. After adjustment for potential confounders in multivariate regression models, longer duration of gout and lower adjusted mean fasting serum HDL-C level remained independently predictive of gouty flares. CONCLUSIONS: Low serum high-density lipoprotein cholesterol level was an independent predictor for gouty flares. Whether optimizing serum HDL-C level can benefit patients with gout in terms of reducing gouty flares needs to be addressed by controlled trials.

Neuropsychiatric lupus and reversible posterior leucoencephalopathy syndrome: a challenging clinical dilemma.

Reversible posterior leucoencephalopathy syndrome (RPLS) has been increasingly recognized and reported in the literature. While the condition has been well described in patients with acute hypertension, pre-eclampsia, eclampsia, post-transplantation and chemotherapy, RPLS has been increasingly identified in patients with autoimmune diseases such as systemic lupus erythematosus (SLE). Though experience in the diagnosis and management of RPLS in patients with SLE is likely accumulating, few have systematically worked out the strategy to distinguish RPLS from neuropsychiatric SLE (NPSLE) and lupus-related complications of the central nervous system (CNS). Prompt recognition of, and differentiation between, these conditions is essential since their clinical presentations substantially overlap and yet their management strategy and subsequent outcomes can be entirely different. Indeed, inappropriate treatment such as augmentation of immunosuppression may be detrimental to patients with RPLS. A high index of suspicion of RPLS, prompt magnetic resonance imaging of the brain, including diffusion imaging, exclusion of CNS infection and metabolic derangement, a comprehensive medication review accompanied by timely and aggressive control of blood pressure and seizure are keys to successful management of RPLS. Such treatment strategy ensures a very high chance of total neurological recovery in lupus patients with RPLS.

Comparison of risk factors for obesity in young, nonobese African-American and Caucasian women.

OBJECTIVE: To determine whether specific risk factors for obesity were more evident in young, normal-weight African-American (AA) compared to Caucasian-American (CA) women. DESIGN: Cross-sectional age-matched study. SUBJECTS: Young, nonobese, sedentary AA (n= 13, 22.5y of age, 23.6% body fat) and CA women (n = 11, 21.5y of age, 24.0% body fat). MEASUREMENTS: Aerobic physical fitness (peak VO2), resting metabolic rate (RMR), resting and submaximal exercise fat oxidation rates, total daily energy expenditure (TDEE) by the doubly-labeled water method, physical activity energy expenditure (PAEE), skeletal muscle glycolytic (phosphofructokinase activity (PFK)) and beta-oxidative (beta-hydroxy-acyl CoA dehydrogenase (beta-HADH)) activity, and insulin sensitivity estimated by the insulin-augmented frequently sampled intravenous glucose tolerance test. RESULTS: The AA and CA subjects were similar in age, body mass index and body composition, but the AA women exhibited lower peak VO2. There were no group differences in RMR adjusted for body composition, or in the rates of submaximal exercise energy expenditure or fat oxidation, and no difference in skeletal muscle beta-HADH or PFK activity. The AA women exhibited lower insulin sensitivity and greater acute insulin response to glucose. The mean TDEE for the AA women was only 74% that of the CA women, primarily due to a lower physical activity energy expenditure (AA group: xPAEE = 1,246+/-438 kJ/day; CA group: x= 3,310+/-466 kJ/day. CONCLUSION: These data indicate that PAEE and its correlates of peak aerobic capacity and insulin sensitivity are lower in young, nonobese AA women compared to their CA counterparts.

Representation of Asian Americans in clinical cancer trials.

PURPOSE: The objectives of this study are to analyze the accrual of Asian Americans to National Cancer Institute (NCI)-supported prevention, screening/diagnosis, and treatment trials and to determine if there is proportional ethnic representation. METHODS: Data were obtained on all participants accrued to ongoing prevention and screening/ diagnosis trials and on all patients accrued to treatment trials from 1994 to mid-1998. In the analysis, the percentage of Asian Americans to the total number of trial participants is calculated. For treatment trials, participants were stratified into five age groups: 0-20 years, 21-44 years, 45-54 years, 55-64 years, and 65 or more years. RESULTS: Asian Americans represented 4.8% of subjects accrued in screening/diagnosis trials, 1.8 to 2.2% of subjects in treatment trials, and 0.9% of subjects in prevention trials. Comparison of treatment trial age groups revealed that younger Asian Americans participate significantly more in treatment trials than older Asian Americans. CONCLUSIONS: Asian American accrual in NCI-supported trials is representative of the cancer burden of Asian Americans in the United States. However, Asian Americans 65+ years are underrepresented. Their full participation in cancer trials is justified.

Medical management of stage IV malignant melanoma. Medical issues.

BACKGROUND: Stage IV melanoma is defined by TNM staging as any tumor, any node, and M1, the presence of distant metastasis. The prognosis of Stage IV melanoma is grim. The expectation for 5-year survival is less than 10%. METHODS: The experience with single-agent chemotherapy, combination chemotherapy, and high dose chemotherapy with autologous bone marrow transplantation support are reviewed, as are the results of treatment with interferon and interleukin-2. RESULTS: Chemotherapy with single agents yields up to a 20% response rate. More aggressive treatments with chemotherapy combinations yield approximately 40% responses but have no survival advantage over treatment with single agents. Recombinant alpha-interferon yields an objective response rate of approximately 20%. Results are dose related and require a dose in the range of 12 million U/M2 for optimal response. The results of treatment with interleukin-2 and lymphokine-activated killer cells are promising, but the optimal dose and method of administration need to be confirmed. The interesting appearance of a vitiligo-like depigmentation in some patients who respond to treatment seems to be associated favorably with survival. Gene transfer therapy opens up a new horizon for treatment of metastatic melanoma, and this exciting approach is discussed. CONCLUSIONS: The treatment of metastatic melanoma is reviewed, including the roles of surgery, radiation therapy, chemotherapy, interferon, interleukin-2, vaccines, and gene transfer therapy.

The future direction of clinical trials.

BACKGROUND: A milestone in the acquisition of medical information was the development of the concept of clinical trials, which has permitted the documentation and codification of treatment results. This has led to significant advances in clinical medicine during the past few decades. METHOD: This article addresses the future of clinical trials from several perspectives. What forces are present in the clinical world that would affect the continuation of clinical trials? What are the influences of cost and participants' attitudes on clinical trials? What developments in basic science may alter the direction of clinical trials? RESULTS: The role of volunteers in the conduct of clinical trials is explored. The entry of gene transfer therapy into clinical trials is discussed. CONCLUSIONS: Clinical trials hold the key to treatment decisions in medicine. Health care planners will look at clinical trial results for the basis of reimbursement or financing. Therefore, as medical professionals, we must be vigilant of the conduct and results of clinical trials. We must be sure of the validity of their results and ensure their applicability to the proper management of patients.

Pain in the cancer patient.

In summary, the ACS has acknowledged the magnitude and severity of the cancer pain problem nationally and recognized that cancer pain can be relieved. It has identified cancer pain control as a priority and has devised programs that emphasize the importance of pain assessment, recognize the availability of pain relief programs, and encourage treatment to achieve optimum pain relief for the cancer patient.

The past, the present, the future.

Lung cancer in women has replaced uterine cancer among the cancers causing the highest mortality in women. However, breast cancer remains a leading cause of death because of increasing incidence. Potential causes for the increase in both these diseases in women will be explored. An exciting development in recent years has been the clarification of the role of oncogenes in carcinogenesis. It appears that some cancers require multiple sequential mutations for malignant transformation to occur. This may be the model for the study of carcinogenesis. These developments in molecular genetics have important implications in screening, diagnosis, prevention, and in treatment strategies. We may be witnessing the beginning of the era of cell differentiation therapy. Retinoids have a potential for impacting on the treatment of neoplasms such as promyelocytic leukemia and oropharyngeal cancers. Understanding of the mechanism of cell differentiation may be forthcoming although molecular genetic studies.

Asymptomatic intrathoracic extramedullary hematopoiesis: a report of three cases.

Extramedullary hematopoiesis (EMH) is observed in people suffering from severe anemia of prolonged duration and appears to be a compensatory mechanism for disturbed medullary hematopoiesis. The hemoglobinopathies (such as thalassemia, spherocytosis, and sickle cell disease), neoplastic diseases such as leukemia and lymphoma, and others, including myelofibrosis and osteitis fibrosa cystica, are associated with EMH. These diseases and their resultant anemia have in common the ability to stimulate erythropoietin production, which in turn may stimulate hematopoiesis in organs of mesenchymal origin. The liver and spleen are the most common sites of EMH; however, other sites, including the falx cerebri, thoracic cavity, retroperitoneal area and pelvis have been reported. When present, intrathoracic EMH is most frequently associated with thalassemia. Spinal cord compression and hemothorax have also been reported as complications of intrathoracic EMH.

Cytogenetic study of Kaposi's sarcoma associated with acquired immunodeficiency syndrome.

We performed cytogenetic studies on direct preparations and short-term cultures from Kaposi's sarcoma cells obtained from malignant pericardial effusion. The patient, a 46-year-old man with human immunodeficiency virus infection, initially presented with metastatic Kaposi's sarcoma. Despite therapy, his tumor proved aggressive, and the patient died of widespread pulmonary involvement nine months after diagnosis. Cytogenetic analysis revealed a predominant karyotype of 48,X,-Y, t(2;7)(q32;q36), +der(5)t(5;15)(q?15;q?15), -7, +del(7)(p15), +del(7)(p15), +der(8)t(8;D or G)(q24;p11.2), del(10)(p13), dup(12)(q24), t(18;20)(q21;q13). This case is described in relation to other published cytogenetic studies of this tumor.