Correction to: Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice.

A sentence under 'Results' heading in the Abstract section was published incorrectly. The correct sentence should read as follows.

Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice.

INTRODUCTION: This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data. MATERIALS AND METHODS: Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile. RESULTS: A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2- patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%). CONCLUSIONS: Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.

Effect of protein source during weight loss on body composition, cardiometabolic risk and physical performance in abdominally obese, older adults: a pilot feeding study.

OBJECTIVES: The purpose of this pilot study was to begin to examine the effect of dietary protein source (soy protein versus non-soy protein) during weight loss on body composition, and cardiometabolic and functional decline risk factors in older, abdominally obese adults. DESIGN: Two-arm, single-blind, randomized, controlled trial. SETTING: Wake Forest School of Medicine, Winston-Salem NC 27157, USA. PARTICIPANTS: 25 older (68.4±5.5 years, 88% female), abdominally obese (BMI: 35.1±4.3 kg/m2; WC: 101.4±13.1 cm) men and women were randomized to participate in the study. INTERVENTION: A 12-week weight loss intervention, with participants randomized to consume soy protein-based meal replacements (S; n=12) or non-soy protein-based meal replacements (NS; n=12), in addition to prepared meals, and all participants targeted to receive an individualized caloric deficit of 500 kcal/day. MEASUREMENTS: Body weight and composition (assessed via DXA and CT), conventional biomarkers of cardiometabolic risk, and physical performance measures were assessed pre- and post-intervention. Additional endpoints of feasibility (accrual, participation, retention, compliance, and safety) are reported. RESULTS: A total of 24 participants (87% female) completed the study (96% retention) and lost an average of 7.8±3.0 kg over the 12-week period, with no difference seen between groups (p=0.83). Although nearly all measures of global and regional body composition were significantly reduced following the 12-week intervention, differences were not observed between groups. Among cardiometabolic risk factors and physical performance measures, only diastolic blood pressure was significantly lower in the NS group compared to the S group (66.7±2.7 mmHg vs 73.5±2.7 mmHg, respectively; p=0.04). Interestingly, in groups combined, despite significant reductions in body weight and lean mass, no significant changes in 400-meter walk time (+5.3±43.4 s), short physical performance battery score (+0.1±1.0), grip strength (-0.3±3.2 kg), or relative knee extensor strength (-0.0±0.0 N/m/cm3 thigh muscle volume) were observed. CONCLUSIONS: Data presented here suggest that a 12-week weight loss intervention, which incorporates S and NS meal replacement products, is associated with clinically significant weight loss and improvements in several parameters of cardiometabolic risk and unchanged physical function and strength. RESULTS do not differ by protein source and suggest that soy protein is at least as good as other protein sources for weight loss during low-calorie dietary interventions in older adults.

Postcrystallization Analysis of the Irreproducibility of the Human Intrinsic Factor-Cobalamin Complex Crystals.

Approximately 15% (w/w) of human intrinsic factor (IF) is comprised of carbohydrate side chains, making crystallization problematic. In addition, IF is sensitive to proteolysis. To understand the role of these factors in crystallization, we carried out dynamic light scattering studies and assessed their correlation with crystallization. The packing of the IF-cobalamin complex and the known properties of the protein in solution were also analyzed to explore the irreproducibility of the IF-cobalamin complex crystals and the difficulty in obtaining apo-IF crystals suitable for crystallographic analysis. The results indicate that although glycosylation may in general be inhibitory for crystallization, time-dependent proteolysis appears to play a much more important role in the process of crystallization of IF. Thus, the presence of cobalamin and of domain fragments that can form incomplete dimers lacking one of two ß-domains appears to promote the crystallization of IF.

Effects of dietary protein on the composition of weight loss in post-menopausal women.

OBJECTIVES: To determine whether a hypocaloric diet higher in protein can prevent the loss of lean mass that is commonly associated with weight loss. DESIGN: An intervention study comparing a hypocaloric diet moderately high in protein to one lower in protein. SETTING: Study measurements were taken at the Wake Forest University General Clinical Research Center (GCRC) and Geriatric Research Center (GRC). PARTICIPANTS: Twenty-four post-menopausal, obese women (mean age = 58 +/- 6.6 yrs; mean BMI = 33.0 +/- 3.6 kg/m2). INTERVENTION: Two 20-week hypocaloric diets (both reduced by 2800 kcal/wk) were compared: one maintaining dietary protein intake at 30% of total energy intake (1.2-1.5 g/kg/d; HI PROT), and the other maintaining dietary protein intake at 15% of total energy (0.5-0.7 g/kg/d; LO PROT). The GCRC metabolic kitchen provided lunch and dinner meals which the women picked up 3 days per week and ate outside of the clinic. MEASUREMENTS: Body composition, including total body mass, total lean mass, total fat mass, and appendicular lean mass, assessed by dual energy x-ray absorptiometry, was measured before and after the diet interventions. RESULTS: The HI PROT group lost 8.4 +/- 4.5 kg and the LO PROT group lost 11.4 +/- 3.8 kg of body weight (p = 0.11). The mean percentage of total mass lost as lean mass was 17.3% +/- 27.8% and 37.5% +/- 14.6%, respectively (p = 0.03). CONCLUSION: Maintaining adequate protein intake may reduce lean mass losses associated with voluntary weight loss in older women.

Crystal structure of human intrinsic factor: cobalamin complex at 2.6-A resolution.

The structure of intrinsic factor (IF) in complex with cobalamin (Cbl) was determined at 2.6-A resolution. The overall fold of the molecule is that of an alpha(6)/alpha(6) barrel. It is a two-domain protein, and the Cbl is bound at the interface of the domains in a base-on conformation. Surprisingly, two full-length molecules, each comprising an alpha- and a beta-domain and one Cbl, and two truncated molecules with only an alpha- domain are present in the same asymmetric unit. The environment around Cbl is dominated by uncharged residues, and the sixth coordinate position of Co(2+) is empty. A detailed comparison between the IF-B12 complex and another Cbl transport protein complex, trans-Cbl-B12, has been made. The pH effect on the binding of Cbl analogues in transport proteins is analyzed. A possible basis for the lack of interchangeability of human and rat IF receptors is presented.

Acute renal failure complicating HELLP syndrome, SLE and anti-phospholipid syndrome: successful outcome using plasma exchange therapy.

Renal disease is very common in patients with systemic lupus erythematosis (SLE) and it may emerge during pregnancy or the post-partum period. Patients with anti-phospholipid syndrome (APS)are also at risk of renal disease. We present a case of acute renal failure in the post-partum period in a patient with SLE and APS. This case illustrates the potential difficulties in reaching a diagnosis in such a patient. It also illustrates the complexities of management and the potential interactions between SLE, Haemolysis, elevated liver enzymes and low platelets syndrome, thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome and APS. We also review the role of plasma exchange therapy in managing our patient.

The use of the Internet as a resource for health information among patients attending a rheumatology clinic.

OBJECTIVES: To determine the proportion of patients attending a rheumatology clinic who have access to a computer with Internet capabilities, to establish how often they search for health information, and how difficult or useful they find this resource. METHODS: We performed a questionnaire-based study of consecutive patients attending a rheumatology clinic in two city teaching hospitals over a 1 week period. Patients were asked if they owned or had access to a computer with Internet capabilities, and if they had searched for information on shopping, holidays, entertainment or health information. Further questions were then directed at the nature of the health information, how useful it was and how easy the patient found it to access the details. Patient demographic data were obtained by case record review. RESULTS: One hundred and forty patients were approached; 138 completed questionnaires were collected. One hundred and one respondents (73%) were female. Median patient age was 58 yr (range 18-84). One hundred and seven (78%) had rheumatoid arthritis, with median disease duration of 8 yr (range 6 months to 49 yr). Sixty (43%) had access to the Internet, mostly at home, and used it most frequently for holiday information. Thirty-seven (27% of all respondents) reported that they had searched for medical information on a median of 2 (range 1-10) occasions in the previous 12 months. Of these, 83% perceived the information as useful, 54% discovered something they had not previously known and 31% reported it was easier than asking their doctor or nurse. Patients searched on-line for information on their arthritis (83%), drug treatment (54%), alternative therapies (31%), diet and arthritis (46%) and patient organizations (11%). No patients recalled being advised to search for information by their doctor or nurse. Patients who searched for medical information were younger (median age 48 vs 62 yr; P<0.001), more likely to be employed (32 vs 16%) and more likely to be married or in a stable relationship (84 vs 66%); there were no differences in sex distribution, diagnosis, disease duration or social deprivation. CONCLUSIONS: One in four patients attending our rheumatology clinic had searched the Internet for medical information in the last 12 months. Almost one-third found it easier than asking their health-care professional. Further studies are required to explore the wider application of this resource and to determine the validity and reliability of the information obtained.

Illiteracy in rheumatoid arthritis patients as determined by the Rapid Estimate of Adult Literacy in Medicine (REALM) score.

OBJECTIVES: To determine the prevalence of illiteracy in a cohort of rheumatoid arthritis (RA) patients and the impact of illiteracy on disease severity and function. METHODS: We performed a prospective cross-sectional study with case record review of 127 consecutive patients with RA attending one centre. All patients completed the Rapid Estimate of Adult Literacy in Medicine (REALM) screening test. This 66-word recognition test provides an estimate of reading level in less than 3 min. Demographic data were collected by interview and case record review. Function was assessed with the Health Assessment Questionnaire (HAQ) and depression with the Hospital Anxiety and Depression (HAD) scale, both sent prior to clinic attendance. Social deprivation was assessed with the Carstairs index. RESULTS: Four patients refused to participate. Of these, three stated they were unable to read. Ninety-seven women and 26 men agreed to be interviewed. All but two were Caucasian. Median age was 56 yr (range 19-77 yr) and median disease duration was 10 yr (range 1-60 yr). Median number of previous disease-modifying anti-rheumatic drugs (DMARDs) was two. Eighteen (15%) patients were functionally illiterate, with a REALM score of less than 60. Sex, age, disease duration and numbers of joint replacements and previous DMARDs were not influenced by illiteracy. Illiteracy led to more anxiety (P=0.011), but did not affect HAQ score (P>0.5). Illiteracy was more common in the deprived (P=0.0064). Illiterate patients had three times more hospital visits compared with age- and sex-matched RA controls over the previous 12 months. CONCLUSIONS: One in six of our patient population are illiterate and would struggle to cope with patient education materials and prescription labels. These patients had significantly more hospital visits but equal function, suggesting that additional resources be directed towards these individuals. The REALM test is quick and easy to administer and allows us to identify patients who may require more appropriate literature.

When typical is atypical: mycobacterial infection mimicking cutaneous vasculitis.

Patients with systemic lupus erythematosus (SLE) who present with skin disease pose the clinician with diagnostic challenges. The skin disease can reflect an increase in systemic disease activity suggested by other features of active lupus and, as such, usually responds well to more aggressive immunosuppressive therapy. Other possibilities of skin disease include drug eruptions, skin disease unrelated to SLE and, more rarely, opportunistic skin infection. In patients who show a poor response to more aggressive immunosuppressive therapy, consideration must be given to the possibility of opportunistic infection. A high index of suspicion will allow prompt treatment. We describe two patients with SLE who developed cutaneous atypical mycobacterial infection during immunosuppressive therapy. The diagnosis of cutaneous vasculitis was considered in both cases, but subsequent skin biopsy revealed the correct diagnosis. This report illustrates the importance of skin biopsy in patients with suspected cutaneous lupus who are not responding to immunosuppressive therapy.

Can intervention modify adverse lifestyle variables in a rheumatoid population? Results of a pilot study.

BACKGROUND: Rheumatoid arthritis (RA) is associated with significant excess morbidity and mortality. Cardiovascular disease is the commonest cause of premature death in patients with RA. In recognition of this, blood pressure, weight, and smoking history are routinely ascertained in the clinic and appropriate advice and treatment started. AIMS: To ascertain if attending a specialist nurse, in addition to routine medical care, would increase the success in dealing with lifestyle variables in a cohort of patients with RA. METHODS: Twenty two consecutive patients starting treatment with the disease modifying antirheumatic drug (DMARD) sulfasalazine were invited to attend an additional clinic dealing with lifestyle factors every 12 weeks over a 48 week follow up. Smoking and alcohol history, baseline demographic and metrology assessments were determined for all patients. Body mass index (BMI) was calculated, blood pressure recorded, function assessed by the Health Assessment Questionnaire (HAQ), and social deprivation determined by the Carstairs Index. Patients were advised on exercise and diet, and serum cholesterol was measured. RESULTS: Twenty women and two men, with a mean age of 52 years and mean disease duration of five years, were enrolled. Eight patients smoked and, unfortunately, none were persuaded to discontinue. Fifteen of the cohort were already taking regular exercise; one additional patient began swimming regularly. At baseline, 10 patients were found to have a high cholesterol, with a mean of 6.8 mmol/l. A 14% reduction in mean cholesterol was achieved by dietary modification, and three patients merited statin treatment. Obesity is a major problem in our population and 15 of the patients had grade I obesity with a mean BMI of 30.6; five of these gained a further 4.5 kg. Six patients with previously untreated hypertension were identified, but unfortunately five remained hypertensive and only two had received anti-hypertensive drugs. CONCLUSIONS: Educating patients in order to change lifestyle habits and influence outcome is a long term challenge facing all healthcare workers. In our cohort, most adverse lifestyle factors had already been recognised and discussed by the general practitioner or at prior clinic visits. Additional advice and input led to only modest improvement.

Minocycline induced lupus: case series in the West of Scotland.

OBJECTIVE: To describe the clinical symptoms and serology of drug-induced lupus in patients treated with the semisynthetic tetracycline derivative, minocycline. METHODS: For a 5-year period, all consultant rheumatologists and dermatologists in the West of Scotland were asked to report any suspected cases of a lupus-like syndrome to one center. Twenty cases were identified on the basis of arthritis, positive antinuclear factor and at least one other extraarticular feature following treatment for acne with minocycline. Case histories were reviewed to determine any demographic, clinical, or serological correlations. RESULTS: Minocycline had been prescribed for a mean of 25 months for the 20 patients identified with drug-induced lupus; 15 were female, 5 were male with a mean age of 24 years. All patients had arthritis and most had at least one other extraarticular feature including lethargy, myalgia, fevers, Raynaud's phenomenon, abdominal pain, and butterfly rash. None had renal involvement. All symptoms resolved at a mean of 15.7 weeks after discontinuation of minocycline treatment. CONCLUSIONS: Minocycline is widely used in the treatment of acne and increasingly in the treatment of rheumatic diseases. Although the absolute risk of developing drug-induced lupus is relatively low, it has been estimated that current use of minocycline is associated with an 8.5 fold increased risk of developing a lupus-like syndrome. Prescribing physicians must be vigilant for any of the characteristic symptoms to avoid unnecessary morbidity, investigations, and therapy.

Transfer of cobalamin from intrinsic factor to transcobalamin II.

The process is obscure by which cobalamin (Cbl) in the endocytosed intrinsic factor (IF)-cobalamin (Cbl) complex is released and transferred to transcobalamin II (TCII) within the enterocyte. Using recombinant IF and TCII, binding of Cbl to IF at pH 5.0 was 70% of binding at pH 7.0, whereas for TCII alone, the value was only 12%. TCII binding activity was lost rapidly at lower pH, but this was not due to protease action. TCII incubated at pH 5.0 with cathepsin L was degraded and could not subsequently bind Cbl. Thus, transfer from IF to TCII is unlikely to occur within an acid compartment. Only 13-15% of bound Cbl was released at pH 5.0 and pH 6.0 from either rat IF, human IF, or human TCII. The K(a) of human or rat IF at pH 7.5 was 2.2 nM; for TCII, the value was 0.34 nM. At pH 7.5, Cbl transfers from IF to TCII, but only to a limited extent (21%), as detected by nondenaturing electrophoresis. Transfer of Cbl from IF to TCII could not be demonstrated at pH values of 5.0 or 6.0. Thus, luminal transfer of Cbl between IF and TCII is likely to be limited, but is possible. The most likely mechanism for intracellular transfer of Cbl from IF to TCII involves initial lysosomal proteolysis of IF, with subsequent Cbl binding to TCII in a more neutral cellular compartment.

Acute severe hepatitis with coagulopathy: An unusual presentation of Kawasaki syndrome in association with Epstein-Barr virus.

The first case of Kawasaki syndrome presenting as acute severe hepatitis with coagulopathy, in association with an acute Epstein-Barr virus infection is reported. This case supports the hypothesis that Epstein-Barr virus may play a role in the etiology of Kawasaki syndrome and serves as a reminder that a diagnosis of Kawasaki syndrome should be considered for a persistently febrile child, even in the face of an atypical presentation.

Production of gastric intrinsic factor, transcobalamin, and haptocorrin in opossum kidney cells.

Opossum kidney epithelial cells were shown previously to synthesize and secrete two cobalamin (Cbl)-binding proteins, presumed to be haptocorrin (Hc) and transcobalamin II (TCII). The present study examines the hypothesis that renal tubular cells also produce intrinsic factor (IF), and this production provides an explanation for the presence of IF in urine. By using antisera raised against human IF and against TCII, the presence of TCII was confirmed, and that of IF discovered in the media of opossum kidney (OK) cells in culture. The apparent molecular weight of IF and TCII was 68 and 43 kDa, respectively. Immunoreactivity on Western blot of the putative IF protein was blocked by recombinant human IF. When proteins secreted into the media were separated electrophoretically under nondenaturing conditions after binding with [(57)Co]Cbl, a broad major band migrated at a relative front independently of recombinant IF or TCII, and probably represents Hc, as the Cbl binding is blocked by cobinamide. Small amounts of bound [(57)Co]Cbl migrated in the position of both IF and TCII, when cobinamide was present. The presence of IF and TCII in OK cells was confirmed by immunohistology. Specific reactivity for IF (blocked by recombinant IF) was found in proximal tubules of opossum kidney, but not in other portions of the nephron, confirming the ability of anti-human IF antiserum to detect opossum IF. A 732-bp fragment of IF, nearly identical in sequence to rat IF, was isolated by RT-PCR from opossum kidney mRNA, and Western blot confirmed the presence of IF protein. The presence of IF was also documented in rat kidney by isolation of an RT-PCR fragment, immunocytochemistry, and Western blot. IF should be added to the list of renal (proximal) tubular antigens that are shared by other epithelia.