Trastuzumab interruption and treatment-induced cardiotoxicity in early HER2-positive breast cancer

Breast Cancer Research and Treatment - Trastuzumab improves outcomes among patients with HER2-positive breast cancer but is associated with a risk of treatment-induced cardiotoxicity (TIC). It is...     

Evaluation of screening tests for detecting Chlamydia trachomatis: bias associated with the patient-infected-status algorithm

In recent years, the evaluation of nucleic acid amplification tests (NAATs) for detecting Chlamydia trachomatis and Neisseria gonorrhea is based on a methodology called the patient-infected-status algorithm (PISA). In the simplest version of PISA, 4 test-specimen combinations (comparator tests) are used to define the gold standard. If a person shows a positive result by any 2 or more of these 4 comparator tests, the person is classified as infected; otherwise, the person is considered to be uninfected. A new test is then compared with this diagnostic algorithm. PISA-based sensitivity and specificity estimates of nucleic acid amplification tests have been published in the medical and microbiologic literature and have been included in FDA-approved package inserts of NAATs for detecting C. trachomatis. Using simulations, we compare 2 versions of the patient-infected-status algorithm with latent-class models and an imperfect gold standard. We show that the PISA can produce highly biased test-performance parameter estimates. In a series of simulated scenarios, none of the 95% confidence intervals for PISA-based estimates of sensitivity and prevalence contained the true values. In addition, the PISA-based estimates of sensitivity and specificity change markedly as the true prevalence changes. We recommend that PISA should not be used for estimating the sensitivity and specificity of tests.     

The prognostic significance of subsyndromal delirium in elderly medical inpatients

OBJECTIVES: To determine the prognostic significance of subsyndromal delirium (SSD) presentations. DESIGN: Cohort study. SETTING: University-affiliated primary acute care hospital. PARTICIPANTS: One hundred sixty-four elderly medical inpatients who did not meet Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) criteria for delirium during the first week after admission were classified into three mutually exclusive groups. The first group, prevalent SSD, included those who had two or more of four core symptoms of delirium (clouding of consciousness, inattention, disorientation, perceptual disturbances) at admission. The second group, incident SSD, included those who did not meet criteria for prevalent SSD but displayed one or more new core symptoms during the week after admission. The third group had no prevalent or incident SSD. The three groups were followed up at 2, 6, and 12 months. MEASUREMENTS: Outcomes (length of stay, symptoms of delirium (Delirium index), cognitive (Mini-Mental State Examination) and functional status (instrumental activities of daily living), and mortality) were compared using univariate techniques and multivariate regression models that adjusted for age, sex, marital status, living arrangements before admission, comorbidity, clinical and physiological severity of illness, and dementia status and severity. RESULTS: Patients with prevalent SSD had longer acute care hospital stay, increased postdischarge mortality, more symptoms of delirium, and a lower cognitive and functional level at follow-up than patients with no SSD. Most of the findings for incident SSD were similar but not statistically significant. Patients with prevalent or incident SSD had risk factors for DSM-defined delirium. CONCLUSION: SSD in elderly medical inpatients appears to be a clinically important syndrome that falls on a continuum between no symptoms and DSM-defined delirium.     

Colonic Perforation in Graft Versus Host Disease: A Case Report

Graft versus host disease (GVHD) is a phenomenon that occurs after allogeneic bone marrow transplants. Gastrointestinal (GI) manifestations of acute GVHD are common, but severe GI GVHD complications, such as bowel perforation, occur rarely and necessitate surgical intervention. To our knowledge, there are no recorded cases of colonic perforation resulting from GVHD with negative cultures for infectious agents such as cytomegalovirus. We present a case of large bowel perforation due to GVHD.     

Atomised intranasal midazolam spray as premedication in pediatric patients: comparison between two doses of 0.2 and 0.3?mg/kg

Purpose

Midazolam premedication administered by the intranasal route is noninvasive with good bioavailability. Atomised intranasal midazolam spray ensures accurate drug dosage and better patient acceptability, with rapid onset of action and virtually complete absorption.

Methods

Sixty pediatric patients scheduled for elective surgeries were administered atomised intranasal midazolam. Two doses of midazolam, of 0.2 and 0.3?mg/kg, were compared. Children were observed for achieving satisfactory sedation and separation scores, and face mask acceptance.

Results

At 10 and 20?min of nasal administration, 70 and 76% of the children, respectively, in the 0.3?mg/kg dose group, while 40 and 63% of the children, respectively, in the 0.2?mg/kg group were adequately sedated. Similarly, at 10 and 20?min after administration, 66.6 and 73.3% of children, respectively, in the 0.3?mg/kg group, and 30 and 60% in the 0.2?mg/kg group were easily separated from their parents. With regard to face mask acceptance, 33.3% of patients in the 0.3?mg/kg group and 16.6% in the 0.2?mg/kg group accepted the mask easily.

Conclusion

Atomised midazolam at 0.3?mg/kg is safe, and achieves faster sedation and better separation scores as compared to 0.2?mg/kg.     

Multiple supernumerary teeth in two brothers: a case report

Supernumerary teeth (hypersontia) are relatively common in the general population and occur more frequently in patients with a family history of such teeth. Supernumerary teeth have been reported in many genetic syndromes, but multiple supernumerary teeth occurring as an isolated non-syndromic trait are rare. This article describes a rare non-syndromic variety of multiple impacted supernumerary teeth in two brothers.     

A model system for studying inhibin.

We report here a sensitive model for studying inhibin-like activity in crude ovine testicular extracts (CoTE). The administration of CoTE in 25-100 mg amounts to 35-day-old immature male rats, orchidectomized just prior to use, resulted in the prevention of a rise in plasma FSH levels, seen 10 h post-treatment. In a second model, CoTE was injected at 1000 h of day 35 to a group of rats that was castrated 12-24 h prior to injection, and the animals were sacrificed 6 h later; plasma FSH levels were found to be significantly suppressed. CoTE, administered subcutaneously, both in multiple doses and as a single injection, was found to be equally effective. A single injection suppressed FSH levels within 3-6 h while LH levels were unaffected. The suppressive effect was dose-dependent, reaching a maximum value at doses of 100 mg CoTE and above. FSH levels could not be suppressed below the tonic level, either by the administration of a single large dose of CoTE, or by repetitive injections of maximal doses of CoTE at 3 h intervals. The suppression in FSH levels caused by a single injection of CoTE waned with time and totally disappeared by 36h. CoTE was prepared by the heat treatment (55 C for 30 min) of an aqueous extract of ovine testis, followed by centrifugation and ether extraction of the supernatant. The aqueous layer was then dialyzed and lyophilized. The lyophilized material was found to be free of testosterone, as measured by a specific radioimmunoassay, indicating that the active factor is a heat-stable, lyophilizable, nondialyzable material, free of contamination by testosterone and probably by other steroids.     

BRCA-mutation-associated fallopian tube carcinoma: a distinct clinical phenotype?

OBJECTIVE: To compare clinical and histologic features between fallopian tube cancers in women with germline BRCA mutations and sporadic cases. METHODS: Twenty-eight patients with fallopian tube cancer had BRCA mutation testing using multiplex polymerase chain reaction and protein truncation testing. Histologic slides were reviewed by 2 pathologists, and immunohistochemical staining for p53, ki67, estrogen receptor, and progesterone receptor was performed on carcinomas and dysplastic and benign tubal epithelia. RESULTS: Twelve of 28 (43%) women had BRCA mutations: 11 BRCA1, 1 BRCA2. Excluding 4 cases found at prophylactic surgery, the median age of diagnosis of BRCA mutation carriers was 57 years compared with 65 years among sporadic cases (P = .09). Patients with BRCA-associated fallopian tube cancer had a median survival time of 68 months compared with 37 months when compared with sporadic cases (P = .14). Both groups had predominantly advanced stage, high grade, serous fallopian tube cancers. No patient had exclusively proximal disease. Occult fallopian tube cancer diagnosed at prophylactic surgery in BRCA mutation carriers was exclusively distal. "Skip" areas of high-grade dysplasia were only seen in 2 patients, both of whom were BRCA mutation carriers. There were no differences in the immunohistochemical staining for p53, ki67, estrogen receptor or progesterone receptor in carcinomas and dysplastic or benign epithelia of patients with or without BRCA mutations. Overexpression of p53 was commonly seen in fallopian tube cancers and dysplastic epithelium, but rarely noted in benign epithelium. CONCLUSION: Fallopian tube cancer is part of the BRCA mutation phenotype and seems to share many clinical features with sporadic fallopian tube cancers, including no exclusively proximal disease. The presentation of BRCA-associated fallopian tube cancers may, however, occur at a younger age and have an improved survival.