Latent Rheumatic Heart Disease: Outcomes 2 Years After Echocardiographic Detection

Screening with portable echocardiography has uncovered a large burden of latent rheumatic heart disease (RHD) among asymptomatic children in endemic regions, the significance of which remains unclear. This study aimed to determine the 2-year outcomes for children with latent RHD diagnosed by echocardiographic screening. Children identified with latent RHD enrolled in a biannual follow-up program. Risk factors for disease persistence and progression were examined. Of 62 children, 51 (82 %) with latent RHD had a median follow-up period of 25 months. Of these 51 children, 17 (33.3 %) reported an interval sore throat or symptoms consistent with acute rheumatic fever (ARF). Of 43 children initially classified as having borderline RHD, 21 (49 %) remained stable, 18 (42 %) improved (to no RHD) and 4 (10 %) worsened to definite RHD. Of the 8 children initially classified as having definite RHD, 6 (75 %) remained stable, and 2 (25 %) improved to borderline RHD. Two children had confirmed episodes of recurrent ARF, one of which represented the sole case of clinical worsening. The risk factors for disease persistence or progression included younger age (p = 0.05), higher antistreptolysin O titers at diagnosis (p = 0.05), and more morphologic valve abnormalities (p = 0.01). After 2 years, most of the children had a benign course, with 91 % remaining stable or showing improvement. Education may improve recognition of streptococcal sore throat. Longer-term follow-up evaluation, however, is warranted to confirm disease progression and risk factor profile. This could help tailor screening protocols for those at highest risk.     

The role of p53 in suppression of KSHV cyclin-induced lymphomagenesis

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a cyclin D homolog, K cyclin, that is thought to promote viral oncogenesis. However, expression of K cyclin in cultured cells not only triggers cell cycle progression but also engages the p53 tumor suppressor pathway, which probably restricts the oncogenic potential of K cyclin. Therefore, to assess the tumorigenic properties of K cyclin in vivo, we transgenically targeted expression of K cyclin to the B and T lymphocyte compartments via the E micro promoter/enhancer. Around 17% of E micro -K cyclin animals develop lymphoma by 9 months of age, and all such lymphomas exhibit loss of p53. A critical role of p53 in suppressing K cyclin-induced lymphomagenesis was confirmed by the greatly accelerated onset of B and T lymphomagenesis in all E micro -K cyclin/p53(-/-) mice. However, absence of p53 did not appear to accelerate K cyclin-induced lymphomagenesis by averting apoptosis: E micro -K cyclin/p53(-/-) end-stage lymphomas contained abundant apoptotic cells, and transgenic E micro -K cyclin/p53(-/-) lymphocytes in vitro were not measurably protected from DNA damage-induced apoptosis compared with E micro -K cyclin/p53(wt) cells. Notably, whereas aneuploidy was frequently evident in pre-lymphomatous tissues, end-stage E micro -K cyclin/p53(-/-) tumors showed a near-diploid DNA content with no aberrant centrosome numbers. Nonetheless, such tumor cells did harbor more restricted genomic alterations, such as single-copy chromosome losses or gains or high-level amplifications. Together, our data support a model in which K cyclin-induced genome instability arises early in the pre-tumorigenic lymphocyte population and that loss of p53 licenses subsequent expansion of tumorigenic clones.     

An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions

Background.

BRCA1 and BRCA2 germline mutations are associated with an elevated risk for pancreas adenocarcinoma (PAC). Other BRCA-associated cancers have been shown to have greater sensitivity to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors with better clinical outcomes than in sporadic cases; however, outcomes in BRCA-associated PAC have not been reported.

Methods.

Patients with a known BRCA1 or BRCA2 mutation and a diagnosis of PAC were identified from the Gastrointestinal Oncology Service, Familial Pancreas Cancer Registry, and Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center.

Results.

Fifteen patients, five male, with a BRCA1 (n = 4) or BRCA2 (n = 11) mutation and PAC and one patient with a BRCA1 mutation and acinar cell carcinoma of the pancreas were identified. Seven female patients (70%) had a prior history of breast cancer. Four patients received a PARP inhibitor alone or in combination with chemotherapy; three demonstrated an initial radiographic partial response by Response Evaluation Criteria in Solid Tumors whereas one patient had stable disease for 6 months. Six patients received platinum-based chemotherapy first line for metastatic disease; five of those patients had a radiographic partial response.

Conclusion.

BRCA mutation–associated PAC represents an underidentified, but clinically important, subgroup of patients. This is of particular relevance given the ongoing development of therapeutic agents targeting DNA repair, which may potentially offer a significant benefit to a genetically selected population. We anticipate that further study and understanding of the clinical and biologic features of BRCA-mutant PAC will aid in the identification of tissue biomarkers indicating defective tumor DNA repair pathways in sporadic PAC.     

Complaints handling in hospitals: an empirical study of discrepancies between patients' expectations and their experiences

Background  

Many patients are dissatisfied with the way in which their complaints about health care are dealt with. This study tested the assumption that this dissatisfaction consists – in part at least – of unmet expectations.     

Intensive care information system reduces documentation time of the nurses after cardiothoracic surgery

OBJECTIVE: Nowadays, registration of patient data on paper is gradually being replaced by registration using an intensive care information system (ICIS). The aim of this study was to evaluate the effect of the use of an ICIS on nursing activity. DESIGN: Randomized controlled trial with a crossover design. SETTING: An 18-bed medical-surgical ICU in a teaching hospital. PATIENTS, NURSES AND INTERVENTIONS: During a 6week period 145 consecutive adult patients admitted to the ICU after uncomplicated cardiothoracic surgery were randomized into two groups: for one group the documentation was carried out using a paper-based registration (Paper), in the second group an ICIS was used for documentation. MEASUREMENTS AND RESULTS: The nursing activities for these patients were studied during two separate periods: the admission period and the registration phase (the period directly following the admission procedure). The duration of the admission procedure was measured by time-motion analysis and the nursing activities in the registration phase were studied by work sampling methodology. All nursing activities during the registration phase were grouped in four main categories: patient care, documentation, unit-related and personal time. The duration of the admission procedure was longer in the ICIS group (18.1+/-4.1 versus 16.8+/-3.1 min, p<0.05). In the registration phase, a 30% reduction in documentation time (Paper 20.5% of total nursing time versus ICIS 14.4%, p<0.001), corresponding to 29 min (per 8h nursing shift) was achieved. This time was completely re-allocated to patient care. CONCLUSIONS: The use of the present ICIS in patients after cardiothoracic surgery alters nursing activity; it reduces the time for documentation and increases the time devoted to patient care. Electronic supplementary material: is available if you access this article at http://dx.org/10.1007/s00134-002-1542-9. On that page (frame on the left side), a link takes you directly to the supplementary material.     

Furthering patient adherence: A position paper of the international expert forum on patient adherence based on an internet forum discussion

Background  

As the problem of patient non-adherence persists and a solution appears hard to be found, it continues to be important to look for new ways to further the issue. We recently conducted a meta-review of adherence intervention studies which yielded a preliminary agenda for future research, practice and theory development in patient adherence. The objective of the present project was to find out to what extent adherence experts consider this agenda relevant and feasible.     

Occupational exposure to indium: what does biomonitoring tell us?

Background

The industrial uses of indium, a rare metal with no known physiological role in humans, have increased dramatically over the past 15 years.The results of animal toxicity studies showing pulmonary and systemic effects as well as some reports in workers have created a growing concern about the possible occurrence of toxic effects in exposed workers. Validated biomarkers to assess exposure to indium are not available.

Objectives

This work aimed at investigating the kinetics of indium in urine (In-U) and plasma (In-Pl) in workers manufacturing In ingots and mainly exposed to hardly water-soluble In compounds. All nine workers from the In department of a large metallurgical concern participated in the study as well as 5 retired workers and 20 controls.

Methods

Personal breathing zone air was collected throughout the work shift on Monday and Friday. Blood and urine samples were collected, before and after the shift, on the same day as the air sampling and on preshift the next Monday after a non-working week-end. Moreover, rats were given either InCl₃ by intraperitoneal injection or In₂O₃ by pharyngeal aspiration, In was followed in plasma during 120 days and measured in tissues 120 days after exposure.

Results

Higher In-Pl and In-U concentrations were found in both current (range 0.32–12.61 μg/L plasma; 0.22–3.50 μg/g creat) and former (0.03–4.38 μg/L plasma; 0.02–0.69 μg/g creat) workers compared with controls (<0.03 μg/L plasma; <0.02 μg/g creat). Both biological parameters were highly correlated but no correlation was found between In-air (10–1030 μg/m³) and In-Pl or In-U. Normalizing In-U by the urinary creatinine concentration reduced the inter- (from 90% to 70%) and intra-individual variability (from 54% to 35%). In-Pl remained remarkably stable along the working week (inter- and intra-individual variability: 89% and 10%, respectively). Neither In-U nor In-Pl significantly increased during the day or the week. A week-end without occupational exposure was not sufficient to reach the background In-Pl and In-U levels measured in controls. The results of the experimental investigations confirmed the hypothesis that inhalation of hardly soluble In compounds may cause accumulation of In in the body leading to a prolonged “endogenous exposure” from both a lung depot of “insoluble” particles that are progressively absorbed and from a retention depot in other internal organs.

Conclusion

This study shows that in workers exposed to hardly soluble In compounds, In-U and In-Pl are very sensitive to detect exposure and mainly reflect long-term exposure. In-Pl levels are particularly stable for a given individual. In-U might be more influenced than In-Pl by recent exposure. Both parameters remained high years after withdrawal from exposure, indicating a possible endogenous exposure and a prolonged risk of pulmonary and systemic diseases even after work exposure has ceased.     

Hormone modulation: a novel therapeutic approach for women with severe mental illness

OBJECTIVES: Accumulating evidence describes the effects of oestrogen and other gonadal hormones on the central nervous system and, in particular, on the mental state of women. Evidence supporting the psychotherapeutic effects of exogenous oestrogen has started to emerge only over the past two decades. The purpose of the present paper was to provide an overview of different applications of adjunctive hormones, as treatments for symptoms of severe mental illness in women. METHODS: Three case reports are presented: in each case the woman selected had participated in large, double-blind, randomized controlled trials exploring hormone modulation. Case study 1 presents a premenopausal woman with schizophrenia, who received an 8 week trial of daily adjunctive 200 microg transdermal oestradiol. Case study 2 presents a postmenopausal woman with schizophrenia on a 12 week trial of adjunctive raloxifene hydrochloride 120 mg per day. Case study 3 presents a woman with schizoaffective disorder, in the manic phase, who received tamoxifen 40 mg per day for 28 days. RESULTS: Adjunctive oestradiol was associated with an improvement in symptoms of psychosis in a premenopausal woman with schizophrenia; adjunctive raloxifene was associated with an improvement in cognitive functioning in a postmenopausal woman with schizophrenia; and adjunctive tamoxifen was associated with an improvement in symptoms of mania in a woman with schizoaffective disorder. CONCLUSIONS: These findings are consistent with preliminary research trials suggesting that adjunctive hormone modulation is a promising area of gender-specific treatment for serious mental illness.