Germline MUTYH gene mutations are not frequently found in unselected patients with papillary breast carcinoma

MUTYH-associated polyposis (MAP) is an autosomal recessive disease, which predisposes to polyposis and colorectal cancer. There is a trend towards an increased risk of breast cancer in MAP patients, with a remarkable proportion of papillary breast cancers. To determine whether MUTYH mutations are associated with this specific and rare type of breast cancer, 53 unselected patients with papillary breast cancer were analyzed for founder mutations in the MUTYH gene. No germline mutations were identified, indicating that biallelic MUTYH mutations are not a frequent underlying cause for the development of papillary carcinomas of the breast.     

Iron deficiency in patients with solid tumours: prevalence and management in clinical practice

Purpose

The objective of the present study was to describe the prevalence and management of anaemia and iron deficiency (ID) in treatment-naïve patients with solid tumours in Spain and the incidence of anaemia over 4 months of cancer treatment in clinical practice.

Methods

Multicentre, prospective and observational study in newly diagnosed cancer patients. Data on anaemia and iron parameters and its management were collected prior to the initiation of chemotherapy, at each cycle of chemotherapy and after 4 months of treatment. The main outcomes of the study were the prevalence of anaemia at baseline, its incidence during cancer treatment and the prevalence of absolute ID (AID) and functional ID (FID) prior to chemotherapy initiation.

Results

A total of 295 patients were included in the study. Anaemia was present at diagnosis in 38.6 % of patients and was treated only in 32.5 % of those. A total of 106 patients (60.2 %) without anaemia at baseline developed anaemia during cancer treatment. Serum ferritin and transferrin saturation data were available for 151 of the patients (51.2 %) included in the study. The overall prevalence of ID was 59 %: 48 patients (31.8 %) presented with AID and 41 patients (27.2 %) presented with FID before starting anti-cancer therapy. Thirty-three of 44 non-anaemic iron-deficient patients did not receive any type of iron supplementation before initiating cancer therapy.

Conclusions

Iron parameters are not commonly measured in newly diagnosed cancer patients. A correct evaluation and early management of ID could reduce the incidence of treatment-related anaemia in cancer patients.     

Effects of chronic exercise on myocardial refractoriness: a study on isolated rabbit heart

Aim: To determine whether chronic physical training increases atrial and ventricular refractoriness in isolated rabbit heart. Methods: Trained rabbits were submitted to a protocol of treadmill running. The electrophysiological parameters of refractoriness investigated in an isolated heart preparation were: (1) atrial effective refractory period (AERP) and atrial functional refractory period and ventricular effective and functional refractory periods (VERP and VFRP) using the extrastimulus technique at four different pacing cycle lengths; (2) the dominant frequency (DF) of ventricular fibrillation (VF). A multi‐electrode plaque containing 256 electrodes and a spectral method were used to obtain the mean, maximum and minimum DF of VF. Sinus cycle length of the isolated hearts was determined as an electrophysiological parameter of training. In vivo heart rate, myocardial heat shock proteins (HSP60) and inducible nitric oxide synthase were also determined in some animals as electrophysiological and biochemical markers of training respectively. Results: VERP and VFRP were longer in the trained group than in the control group. The mean DF of VF was lower in the trained group than in the control group. Despite the fact that training did not significantly modify the AERP, it tended to be longer in the trained group (P = 0.09). Conclusion: Training seems to increase the electrical stability of ventricular myocardium. As the electrophysiological modifications were exhibited in hearts not submitted to extrinsic nervous system or humoral influences, they are, at least in part, intrinsic modifications. These electrophysiological data also suggest that training could protect against reentrant ventricular arrhythmias.     

Anti-GBM nephritis in the mouse: severe proteinuria in the heterologous phase

Summary Highly reproducible anti glomerular basement membrane (GBM) nephritis has been induced in the mouse after a single injection of rabbit or goat antibody against purified homologous GBM. The severity of albuminuria was closely related to the amount of antibody given. With doses of 4 mg or more, low serum albumin concentrations, sometimes accompanied by ascites and oedema, were observed after 1 week. Glomerular injury was characterized by an initial accumulation of polymorphonuclear granulocytes followed by thrombosis and necrosis, the extent of which defined the outcome of the glomerulonephritis. With high doses of antibody the exudative lesions entered a chronic phase, while at doses lower than 2 mg remission of the lesions occurred. Immunofluorescence studies showed prompt linear fixation of the injected anti-bodies to the glomerular capillary wall, accompanied by immediate binding of C3 in a fine granular pattern. Fibrin deposits appeared at 2 h in some glomeruli, increased thereafter, and were present after one day in more than 90% of the glomeruli in mice that had received 4 mg of antibody. This new reproducible model in the mouse is suited for the study of the relationship between activation of mediator systems, histological lesions, and proteinuria.     

Prevalence of Leishmania infantum infection in dogs living in an area of canine leishmaniasis endemicity using PCR on several tissues and serology

We studied and compared the prevalence of Leishmania infection and the seroprevalence and the prevalence of canine leishmaniasis in an area where canine leishmaniasis is endemic. One hundred dogs living on the island of Mallorca (Spain) were studied. In this study, we clinically examined each dog for the presence of symptoms compatible with leishmaniasis, determined the titer of anti-Leishmania antibodies, and investigated the presence of Leishmania DNA by PCR in skin, conjunctiva, and bone marrow samples of each dog. The prevalence of the disease and the seroprevalence were 13 and 26%, respectively. In 63% of the dogs, Leishmania DNA could be detected by PCR in at least one of the tissues studied. The results of positive PCR in the bone marrow, the conjunctiva, and the skin were 17.8, 32, and 51%, respectively. The prevalence of the infection, 67%, was calculated using all animals that were seropositive and/or positive by PCR with any tissue. The results showed that the majority of dogs living in an area where canine leishmaniasis is endemic are infected by Leishmania and that the prevalence of infection is much greater than the prevalence of overt Leishmania-related disease.     

Psychiatric disorders,acne and systemic retinoids: comparison of risks

Background: The link between isotretinoin, treatment of a severe form of acne, and psychiatric disorders remains controversial, as acne itself could explain the occurrence of psychiatric disorders. This study aims at assessing the disproportionality of psychiatric adverse events reported with isotretinoin in the French National PharmacoVigilance Database, compared with other systemic acne treatments and systemic retinoids.

Materials and methods: Data were extracted from the French National PharmacoVigilance Database for systemic acne treatments, systemic retinoids and drugs used as comparators. Each report was subjected to double-blind analysis by two psychiatric experts. A disproportionality analysis was performed, calculating the number of psychiatric ADRs divided by the total number of notifications for each drug of interest.

Results: Concerning acne systemic treatments: all 71 reports of severe psychiatric disorders involved isotretinoin, the highest proportion of mild/moderate psychiatric adverse events was reported with isotretinoin (14.1%). Among systemic retinoids, the highest proportion of severe and mild/moderate psychiatric events occurred with isotretinoin and alitretinoin.

Conclusion: Our study raises the hypothesis that psychiatric disorders associated with isotretinoin are related to a class effect of retinoids, as a signal emerges for alitretinoin. Complementary studies are necessary to estimate the risk and further determine at-risk populations.     

Current thinking on chronic renal allograft rejection: issues, concerns, and recommendations from a 1997 roundtable discussion

Chronic rejection accounts for most renal allograft losses after the first year posttransplantation. On March 24 and 25, 1997, a roundtable of five transplant surgeons, two nephrologists, and one pathologist assembled in Dallas, Texas, to review critical issues surrounding chronic renal allograft rejection. This article summarizes the presentations and relevant discussions of this meeting regarding the cause of chronic rejection, clinical diagnoses, risk factors, future prospects for intervention strategies, and general recommendations for the transplant community. Growing evidence indicates that chronic rejection is the aggregate sum of irreversible immunologic and nonimmunologic injuries to the renal graft over time. A history of acute rejection episodes and inadequate immunosuppression, likely attributable to inconsistent cyclosporine exposure or poor patient compliance, are among the most recognizable immunologic risk factors for chronic rejection. Donor organ quality, delayed graft function, and other donor and recipient variables leading to reduced nephron mass are nonimmunologic factors that contribute to the progressive deterioration of renal graft function. Clinical management of renal transplant recipients should incorporate both immunologic- and nonimmunologic-based intervention strategies aimed at minimizing risk factors to thwart the progression of chronic rejection and improve long-term allograft and patient survival.     

Early neutralizing and glycoprotein B (gB)-specific antibody responses to human cytomegalovirus (HCMV) in immunocompetent individuals with distinct clinical presentations of primary HCMV infection.

BACKGROUND: Antibodies with functional anti-Human Cytomegalovirus (HCMV) activity are likely to be involved in preventing virus dissemination and thus may contribute to minimize the clinical manifestations of infection. OBJECTIVES: To investigate the role of humoral immunity in modulating the clinical expression of primary Human Cytomegalovirus (HCMV) infection in immunocompetent persons. STUDY DESIGN: Neutralizing (NA) and glycoprotein B (gB)-specific antibodies were quantitated in acute-phase and late-convalescence phase sera from 19 individuals who developed either HCMV mononucleosis (12) or oligosymptomatic hepatitis (seven). RESULTS: The levels of NA in sera drawn early after infection were significantly lower in the former patients than in the latter (P=0. 032). This difference was not related to either the total serum IgG levels and anti-HCMV IgGs avidity or to the presence of higher viral loads in blood, as assessed by detecting serum HCMV DNA by PCR, in patients experiencing mononucleosis. Increased NA titers were seen in all available late-convalescence sera. In these sera, median NA levels were not significantly different among the study groups. Antibodies to HCMV gB of both IgG and IgM classes were detected in all acute-phase sera analyzed. Median anti-gB IgG and IgM titers did not differ significantly between study groups. Likewise, the IgG subclass reactivity pattern against gB was found to be similar for both groups. CONCLUSIONS: The data revealed that an intense and early antibody response to gB developed in patients undergoing primary HCMV infection irrespective of the clinical manifestation of the disease. In contrast, a deficient NA response was observed in patients with HCMV mononucleosis versus that observed in patients displaying a milder form of disease-suggesting that the strength of NA response to HCMV generated early after infection might determine the severity of primary HCMV infection.     

Prognostic Significance of Heart Rate Variability During the First 24 Hours of Acute Myocardial Infarction: A 5‐Year Follow‐up Study

Background: The prognostic value of heart rate variability (HRV) measured within the first 24 hours of acute myocardial infarction was assessed in 94 consecutive patients. Methods: The mean of standard deviation of normal R‐R intervals for all 5‐minute segments (SDNN index), the width of the R‐R interval histogram at 10% and 50% of the peak, and three frequency‐domain measures of HRV (low frequency [LF], high frequency [HF], and LF/HF ratio) were calculated from a continuous ECG recording taken within the first hours of admission and their prognostic value for long‐term events was studied. Results: During the follow‐up period (56.7 ± 5.9 months) 6 sudden and 7 nonsudden cardiac deaths occurred. Time‐domain measurements of HRV were lower in patients with sudden death (SDNN index: 27.0 ± 20.2 vs 47.5 ± 20.7 ms in survivors, P < 0.001). LF and HF power, but not the LF/HF ratio, were also inversely associated with sudden death. No significant differences were found between survivors and patients with nonsudden cardiac death. After adjustment for other clinical covariates, LF and HF power remained significantly associated with sudden death. Conclusion: We conclude that heart rate variability measured within the first 24 hours of myocardial infarction is a strong predictor of sudden death during subsequent follow‐up.