Feasibility of collecting tumor samples of breast cancer patients diagnosed up to 50 years ago in the Child Health and Development Studies.

Environmental exposures during pregnancy may increase breast cancer risk for mothers and female offspring. Tumor tissue assays may provide insight regarding the mechanisms. This study assessed the feasibility of obtaining tumor samples and pathology reports from mothers (F0) who were enrolled in the Child Health and Development Studies during pregnancy from 1959 to 1967 and their daughters (F1) who developed breast cancer over more than 50 years of follow-up. Breast cancer cases were identified through linkage to the California Cancer Registry and self-report. Written consent was obtained from 116 F0 and 95 F1 breast cancer survivors to access their pathology reports and tumor blocks. Of those contacted, 62% consented, 13% refused and 24% did not respond. We obtained tissue samples for 57% and pathology reports for 75%, and if diagnosis was made ⩽10 years we obtained tissue samples and pathology reports for 91% and 79%, respectively. Obtaining pathology reports and tumor tissues of two generations is feasible and will support investigation of the relationship between early-life exposures and molecular tumor markers. However, we found that more recent diagnosis increased the accessibility of tumor tissue. We recommend that cohorts request consent for obtaining future tumor tissues at study enrollment and implement real-time tissue collection to enhance success of collecting tumor samples and data.

Options for prandial glucose management in type 2 diabetes patients using basal insulin: addition of a short-acting GLP-1 analogue versus progression to basal-bolus therapy.

Integrating patient-centered diabetes care and algorithmic medicine poses particular challenges when optimized basal insulin fails to maintain glycaemic control in patients with type 2 diabetes. Multiple entwined physiological, psychosocial and systems barriers to insulin adherence are not easily studied and are not adequately considered in most treatment algorithms. Moreover, the limited number of alternatives to add-on prandial insulin therapy has hindered shared decision-making, a central feature of patient-centered care. This article considers how the addition of a glucagon-like peptide 1 (GLP-1) analogue to basal insulin may provide new opportunities at this stage of treatment, especially for patients concerned about weight gain and risk of hypoglycaemia. A flexible framework for patient-clinician discussions is presented to encourage development of decision-support tools applicable to both specialty and primary care practice.

[Substance use associated disorders: frequency in patients with schizophrenic and affective psychoses]. / Substanzbezogene Störungen: Häufigkeit bei Patienten mit schizophrenen oder affektiven Störungsbildern.

BACKGROUND: Alcohol and substance use disorders (ASUD) are considered to be among the most frequent comorbidities in schizophrenic and affective psychoses and have a significant negative influence on their course and prognosis. In the present study patients with diagnosis from the ICD-10 category F2 or F3 were examined regarding a substance use disorder in a multicentre cross-section evaluation at nine psychiatric hospitals in Baden-Württemberg. The aim of this study is to discuss the current research on substance use disorders and psychosis comorbidity regarding the theoretical models by means of collected data. METHODS: The examination of 50 consecutive admissions per centre is based on a shortened version of the European Severity Index (Europ ASI). An initial urine drug screening was carried out with all patients after admission. Statistical assessment was based on percentage distributions, mean values, standard deviations and suitable correlation analysis. RESULTS: The representative sample included 448 patients. A proportion of 169 patients (37.7%) had a dual diagnosis F2 and F1 and a proportion of 144 patients (32.1%) had a dual diagnosis F3 and F1; 64 patients (14.3%) had an F2 diagnosis and 71 patients (15.8%) had an F3 diagnosis without ASUD. Apart from lifetime use of alcohol (n = 268) and tobacco (n = 325) hypnotics/tranquilizers (n = 214), cannabis (n = 156), opioids (n = 71), stimulants (n = 96) and hallucinogens (n = 36) were consumed. The most frequent combination and long-term intake consisted of tobacco, alcohol, hypnotics/tranquilizer, cannabis and psychostimulants especially in men with schizophrenic disorders. Regarding motivation before first substance use general psychological adjustment disorders (51%), peer impact (42%) and unspecific affective symptoms were predominant. CONCLUSIONS: Altogether the present study clearly demonstrates that patients suffering from schizophrenia, affective disorders and ASUD have significantly higher rates of more severe substance use disorders in their psychosocial environment and more suicidal behaviour than patients without substance misuse. The high rate in the cross-sectional prevalence of tobacco, alcohol, cannabis and psychostimulant use calls for more effective drug prevention.

Use of antidepressant medication and risk of type 2 diabetes: results from three cohorts of US adults.

AIMS/HYPOTHESIS: The results of several studies have suggested a potential positive association between use of antidepressant medication (ADM) and incident type 2 diabetes mellitus. We examined this association in three cohorts of US adults. METHODS: We followed 29,776 men in the Health Professionals Follow-up Study (HPFS, 1990-2006), 61,791 women in the Nurses' Health Study I (NHS I, 1996-2008) and 76,868 women in NHS II (1993-2005), who were free of diabetes mellitus, cardiovascular disease or cancer at baseline. The mean baseline ages for participants from the HPFS and NHS I and II were 56.4, 61.3 and 38.1 years, respectively. ADM use and other covariates were assessed at baseline and updated every 2 years. A time-dependent Cox proportional hazards model was used, and HRs were pooled together across the three cohorts. RESULTS: During 1,644,679 person-years of follow-up, we documented 6,641 new cases of type 2 diabetes. ADM use was associated with an increased risk of diabetes in all three cohorts in age-adjusted models (pooled HR 1.68 [95% CI 1.27, 2.23]). The association was attenuated after adjustment for diabetes risk factors and histories of high cholesterol and hypertension (1.30 [1.14, 1.49]), and further attenuated by controlling for updated BMI (1.17 [1.09, 1.25]). Use of selective serotonin reuptake inhibitors and other antidepressants (mainly tricyclic antidepressants) were both associated with an elevated risk of diabetes, with pooled multivariate-adjusted HRs of 1.10 (1.00, 1.22) and 1.26 (1.11, 1.42), respectively. CONCLUSIONS/INTERPRETATION: The results suggest that ADM users had a moderately elevated risk of type 2 diabetes mellitus compared with non-users, even after adjustment for BMI.

Cardiovascular disease risk factors, depression symptoms and antidepressant medicine use in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss in diabetes.

AIMS/HYPOTHESIS: To determine the associations of baseline depression symptoms and use of antidepressant medicines (ADMs) with baseline cardiovascular disease (CVD) risk factors in Look AHEAD (Action for Health in Diabetes) trial participants. METHODS: Look AHEAD participants (n = 5,145; age 58.7 +/- 6.8 years; BMI 35.8 +/- 5.8 kg/m(2)) were assessed for CVD risk factors (elevated HbA(1c) or insulin use, elevated BP or antihypertensive use, elevated lipid levels or lipid-lowering medication, current smoking, BMI > or = 30 kg/m(2), lower peak exercise capacity assessed as metabolic equivalents [METs], and ankle-brachial index <0.9 or >1.3). Participants also completed the Beck Depression Inventory (BDI) and reported their use of ADMs. RESULTS: Of the participants, 14.7% had BDI scores > or = 11, consistent with mild-moderate depression, and 16.5% took ADMs; 4.4% had both depression markers (i.e. elevated symptom scores and took ADMs). In logistic regression analyses of CVD risk (elevated risk factor or use of medication to control the risk factor), controlled for demographic factors, continuous BDI scores and ADM use were each independently associated with elevated BP (or medication), current smoking, BMI > or = 30 kg/m(2) and lower MET values. ADM use was also associated with elevated serum lipids or use of lipid-lowering medication. CONCLUSIONS/INTERPRETATION: Among Look AHEAD participants, depression symptoms or ADM use on entry to the study were each independently associated with a wide range of CVD risk factors. Future research should assess the temporal dynamics of the relationships of depression symptoms and ADM use with CVD risk factors. TRIAL REGISTRATION: Clinicaltrials.gov NCT00017953 FUNDING: This study is funded by the National Institutes of Health with additional support from the Centers for Disease Control and Prevention.

Improved treatment satisfaction and weight-related quality of life with exenatide once weekly or twice daily.

AIMS: To assess treatment satisfaction and weight-related quality of life (QOL) in subjects with Type 2 diabetes treated with exenatide once weekly (QW) or twice daily (BID). METHODS: In this 52-week randomized, multi-centre, open-label study, 295 subjects managed with diet and exercise and/or oral glucose-lowering medications received either exenatide QW or BID during weeks 1-30; thereafter, subjects receiving exenatide BID were switched to exenatide QW, with 258 total subjects receiving exenatide QW during weeks 30-52. Diabetes Treatment Satisfaction Questionnaire-status (DTSQ-s) and Impact of Weight on Quality of Life-Lite (IWQOL-Lite) were assessed at baseline and weeks 30 and 52. Mean group changes from baseline to week 30 were estimated by ancova; changes from week 30 to week 52 were assessed by Student's t-test. RESULTS: Statistically significant improvements from baseline to week 30 were observed in both treatment groups for DTSQ-s and IWQOL-Lite measures, with significantly greater reduction in perceived frequency of hyperglycaemia and greater satisfaction with continuing treatment in the QW group compared with the BID group. Effect sizes for change in DTSQ-s total scores were 0.84 QW, 0.64 BID; for IWQOL-Lite: 0.96 QW, 0.82 BID. Treatment satisfaction and QOL improved significantly between weeks 30 and 52 for those switching from BID to QW. Occurrence of adverse events did not affect patients' improvements in treatment satisfaction and QOL. CONCLUSIONS: Patients treated with exenatide QW or BID experienced significant and clinically meaningful improvements in treatment satisfaction and QOL. Patients who switched from exenatide BID to exenatide QW administration reported further significant improvements.

Avaliação de parâmetros da regeneração óssea através de processamento de imagens / Evaluation of parameters of bone regeneration by image processing

The aim of this work is to analize the evolution of osteotomies in goat's tibia by image processing...

Growth hormone responses to low-dose physostigmine administration: functional sex differences (sexual diergism) between major depressives and matched controls.

BACKGROUND: Considerable endocrine and non-endocrine evidence supports the hypothesis of increased cholinergic activity relative to noradrenergic activity in major depression. We previously reported functional sex differences (sexual diergism) in hypothalamo-pituitary-adrenal cortical (HPA) hormone responses to the administration of low-dose physostigmine (PHYSO), a cholinesterase inhibitor, in 12 female and eight male unipolar major depressives and 12 female and eight male individually matched control subjects. Because growth hormone (GH) secretion also is influenced by cholinergic mechanisms, we measured GH in the samples from this study. METHOD: Subjects underwent four test sessions 5-7 days apart: PHYSO (8 microg/kg i.v.), arginine vasopressin (AVP) (0.08 U/kg i.m.), PHYSO + AVP and saline control. The AVP was administered as a second stimulus to HPA axis hormone secretion. PHYSO and AVP produced no side-effects in about half the subjects and predominantly mild side-effects in the other half, with no significant patient-control differences. Point biserial correlations between side-effects (absent or present) after PHYSO and the corresponding GH responses were non-significant in all groups. RESULTS: Afternoon baseline GH was significantly higher in the women than in the men, but it was not significantly different between the female or the male patients and their respective matched controls. AVP administration had no effect on GH. PHYSO administration acutely stimulated GH secretion, to a similar degree in the women and men. The depressed patients as a group had a significantly greater average post-PHYSO GH response than did their controls, with a trend toward a significant sex x diagnosis interaction: The female depressives had a significantly greater GH response than their female controls, whereas the male depressives had a similar GH response as their male controls. CONCLUSIONS: These findings suggest sexual diergism (functional sex differences) in baseline and cholinergically stimulated plasma GH measures between major depressives and matched normal controls.

Salvage therapy with voriconazole for invasive fungal infections in patients failing or intolerant to standard antifungal therapy.

BACKGROUND: Invasive fungal infections (IFI), particularly those caused by Aspergillus and other angioinvasive molds, are associated with an excessive mortality despite therapy. METHODS: Voriconazole was prescribed on a compassionate basis to patients with IFI who were intolerant to or who had progressed despite standard therapy. Outcome was determined by protocol-based criteria as established by the consensus definitions (complete response [CR], partial response [PR], stable disease, failure, and intolerance). RESULTS: Forty-five patients were enrolled in a compassionate release program (29 [64%] because of failure of response to standard therapy), between 1998 and 2002. Of the 45 patients enrolled, 35 (78%) had invasive Aspergillus, 3 (7%) had Fusarium, and 2 (4%) had Scedosporium infections. Underlying illnesses were as follows: 13 (29%) solid-organ transplant (SOT), 11 (24%) BMT, and 7 (13%) hematologic malignancy. Site of infection was as follows: 26 (58%) pulmonary, 9 (20%) disseminated, 5 (11%) central nervous system (CNS), and 3 (7%) sinus. Overall response rates were as follows: 9 (20%) CR, 17 (38%) PR, 15 (33%) failure, and 4 (9%) intolerant. Seven of the eight (88%) patients with sinus or CNS disease demonstrated stabilization of the IFI. The median duration of voriconazole therapy was 79 days with 9 (20%) patients receiving over 1 year of therapy. Nine thousand one hundred twenty-eight days of therapy were given with only four serious adverse events in two cases considered possibly or probably drug related. CONCLUSIONS: In this population of severely immunocompromised patients with life-threatening IFI who have failed or were intolerant to standard antifungal therapy, voriconazole demonstrated substantial efficacy and an acceptable level of toxicity.

Expression and cellular localization of a modified type 1 ryanodine receptor and L-type channel proteins in non-muscle cells.

Functional and molecular biological evidence exists for the expression of ryanodine receptors in non-muscle cells. In the present study, RT-PCR and 5'-rapid amplification of cDNA 5'-end (5'-RACE analysis) provided evidence for the presence of a type 1 ryanodine receptor/Ca2+ channel (RyR1) in diverse cell types. In parotid gland-derived 3-9 (epithelial) cells, the 3'-end 1589 nucleotide sequence for a rat RyR shared 99% homology with rat brain RyR1. Expression of this RyR mRNA sequence in exocrine acinar cells, endocrine cells, and liver in addition to skeletal muscle and cardiac muscle, suggests wide tissue distribution of the RyR1. Positive identification of a 5'-end sequence was made for RyR1 mRNA in rat skeletal muscle and brain, but not in parotid cells, pancreatic islets, insulinoma cells, or liver. These data suggest that a modified RyR1 is present in exocrine and endocrine cells, and liver. Western blot analysis showed L-type Ca2+ channel-related proteins in parotid acinar cells, which were of comparable size to those identified in skeletal and cardiac muscle, and in brain. Immunocytochemistry carried out on intact parotid acini demonstrated that the dihydropyridine receptor was preferentially co-localized with the IP3 receptor in the apical membranes. From these data we conclude that certain non-muscle cells express a modified RyR1 and L-type Ca2+ channel proteins. These receptor/channels may play a role in Ca2+ signaling involving store-operated Ca2+ influx via receptor-mediated channels.

Sinusoidal spread of liver metastases from renal cell carcinoma: simulation of diffuse liver disease on MR imaging.

Rarely, hepatic metastases can simulate hepatic infiltrative diseases. We present a case of a patient with advanced metastatic renal cell carcinoma who developed hepatomegaly and clinical signs of hepatocellular injury. On magnetic resonance imaging, the injury simulated a diffuse process, e.g., acute fulminant viral or chemical hepatitis or drug toxicity. Despite its high resolution, magnetic resonance imaging might not depict focal lesions in patients with extensive metastases. In correlation with clinical history, malignant disease should be considered when diffusely abnormal hepatic signal intensity is noted.

BK virus in solid organ transplant recipients: an emerging syndrome.

BK virus is a human polyomavirus associated with a range of clinical presentations from asymptomatic viruria with pyuria to ureteral ulceration with ureteral stenosis in renal transplant patients or hemorrhagic cystitis in bone marrow transplant recipients. Infection of renal allografts has been associated with diminished graft function in some individuals. Fortunately, however, the majority of patients with BK virus infections are asymptomatic. The type, duration, and intensity of immunosuppression are major contributors to susceptibility to the activation of BK virus infection. Histopathology is required for the demonstration of renal parenchymal involvement; urine cytology and viral polymerase chain reaction methods are useful adjunctive diagnostic tools. Current, treatment of immunosuppressed patients with polyomavirus viruria is largely supportive and directed toward minimizing immunosuppression. Improved diagnostic tools and antiviral therapies are needed for polyomavirus infections.

Preventing opportunistic infections after hematopoietic stem cell transplantation: the Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation Practice Guidelines and beyond.

This review presents evidence-based guidelines for the prevention of infection after blood and marrow transplantation. Recommendations apply to all myeloablative transplants regardless of recipient (adult or child), type (allogeneic or autologous) or source (peripheral blood, marrow or cord blood) of transplant. In Section I, Dr. Dykewicz describes the methods used to rate the strength and quality of published evidence supporting these recommendations and details the two dozen scholarly societies and federal agencies involved in the genesis and review of the guidelines. In Section II, Dr. Longworth presents recommendations for hospital infection control. Hand hygiene, room ventilation, health care worker and visitor policies are detailed along with guidelines for control of specific nosocomial and community-acquired pathogens. In Section III, Dr. Boeckh details effective practices to prevent viral diseases. Leukocyte-depleted blood is recommended for cytomegalovirus (CMV) seronegative allografts, while ganciclovir given as prophylaxis or preemptive therapy based on pp65 antigenemia or DNA assays is advised for individuals at risk for CMV. Guidelines for preventing varicella-zoster virus (VZV), herpes simplex virus (HSV) and community respiratory virus infections are also presented. In Section IV, Drs. Baden and Rubin review means to prevent invasive fungal infections. Hospital design and policy can reduce exposure to air contaminated with fungal spores and fluconazole prophylaxis at 400 mg/day reduces invasive yeast infection. In Section V, Dr. Sepkowitz details effective clinical practices to reduce or prevent bacterial or protozoal disease after transplantation. In Section VI, Dr. Sullivan reviews vaccine-preventable infections and guidelines for active and passive immunizations for stem cell transplant recipients, family members and health care workers.

Postmenopausal tubo-ovarian abscess due to Pseudomonas aeruginosa in a renal transplant patient: a case report and review of the literature.

BACKGROUND: Pseudomonas aeruginosa is an uncommon cause of infection in the female genital tract. We report a case of postmenopausal tubo-ovarian abscess (TOA) due to P. aeruginosa in a renal transplant recipient. The presentation included mild abdominal symptoms with rapid progression of peritonitis and surgical abscess drainage. This is the first such case in an organ transplant recipient described in the English literature. METHODS AND RESULTS: Published reports of 1040 cases of TOA were reviewed. The most common features were a history of sexually transmitted disease or pelvic inflammatory disease, and symptoms including abdominal pain and fever. Escherichia coli, Bacteroides spp., and Klebsiella pneumoniae were the most frequently encountered pathogens. Neisseria gonorrhoeae and Chlamydia trachomatis, which are frequently isolated from cervical cultures, are uncommonly isolated from tubo-ovarian abscesses. Forty percent of patients were treated with antibiotics alone, 18.8% with abdominal surgery, and 32% with surgery and antimicrobial therapy. CONCLUSION: This report illustrates the muted presentation and atypical microbiology of gynecologic infection in an organ transplant recipient.

Diffuse desmoplastic breast carcinoma metastases to the liver simulating cirrhosis at MR imaging: report of two cases.

Two patients with breast carcinoma, without a prior diagnosis of liver lesions, had proved desmoplastic hepatic metastases that resembled cirrhosis at magnetic resonance (MR) imaging. The cirrhotic appearance of the livers may have resulted from the hepatotoxic effects of chemotherapy and/or hepatic infiltration by the metastatic tumor itself. Despite its high soft-tissue contrast, MR imaging may fail to depict extensive metastases from breast carcinoma, especially when they simulate other diseases (eg, cirrhosis). Correlation of MR imaging findings with clinical history is mandatory.

Orbital presentations of giant cell arteritis.

BACKGROUND: giant cell arteritis (GCA) is a systemic vasculitis that may affect the optic nerve and cause blindness (e.g. ischemic optic neuropathy). Orbital inflammatory disease, however, is an uncommon presentation of GCA. PURPOSE: to alert clinicians to the orbital presentations of GCA. PATIENTS AND METHODS: a retrospective case series from tertiary care academic ophthalmic referral centers of four patients with orbital manifestations of giant cell arteritis. RESULTS: presentation of cases and review of the literature. In three cases, a temporal artery biopsy was diagnostic of GCA, but in one case, an orbital biopsy was needed to confirm the diagnosis. CONCLUSION: GCA can have orbital manifestations and clinicians should be aware of this unusual presentation of GCA in cases of presumed orbital inflammatory pseudotumor in the elderly.