Search

Introduction: Surgery is an essential part of cancer treatment, particularly for localised solid tumours. Geriatric assessments (GA) with tailored interventions or comprehensive GA (CGA) can identify frailty factors and needs of older adults with cancer, assisting treatment decisions and care strategies to reduce postoperative complications. This systematic review summarises the effects of GA/CGA compared to usual care for older adults with cancer intended for surgery: their impact on treatment decisions, supportive care interventions, postoperative complications, survival, and health-related quality of life (HRQOL)., Materials and Methods: We conducted a systematic search of MEDLINE, EMBASE, CINAHL, and PubMed (January 2000-October 2022) for randomised controlled trials (RCTs) or cohort studies with a comparison group on the effects of GA/CGA in older adults with cancer (≥65 years) intended for surgery. This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Due to heterogeneity in study designs and reporting, a meta-analysis was not possible; results are narratively described., Results: From 12,440 citations, 312 were selected for full-text review. Thirteen studies reporting on 12 trials were included for analysis: four RCTs and eight cohort studies with comparison groups (three prospective, five retrospective). RCTs ranged in sample size (122-475; mean 249), with variability in who performed GA/CGA, disciplines involved, and team integration. Primary outcomes included impact of GA/CGA on postoperative delirium (two studies), Clavien-Dindo (CD) grade II-V postoperative complications (one study), hospital length of stay (one study), and a composite criterion including mortality, functional impairment, and weight loss (one study). All RCTs scored high for risk of bias due to underpowering for their primary outcome; none met their primary endpoint. After adjustment for prespecified factors in secondary analyses, one RCT found GA/CGA significantly reduced the odds of postoperative complications (CD grade I-V) (adjusted-OR: 0.33, 95 %CI: 0.11-0.95; p = 0.05) due to fewer grade I-II complications. One RCT reported no significant difference between groups in HRQOL: intervention patients reported less pain at discharge, but this difference disappeared at three-month follow-up., Discussion: Well-powered, high-quality trials are needed to determine the impact of GA/CGA on optimising surgical treatment decisions, supportive care and postoperative outcomes for older adults with cancer., Competing Interests: Declaration of Competing Interest MA reported serving as the Chair of the COSA Geriatric Oncology Group which involves working with interdisciplinary clinicians and stakeholders to raise the profile and provide a collaborative platform to enhance policy and clinical practice in geriatric oncology in Australia. All other authors reported no conflicts of interest., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Objectives: Children with brain cancer and their families have complex care needs throughout diagnosis, active treatment, long-term survivorship, and the palliative phase of illness. This study aimed to explore the perspectives of Australian specialist clinicians on barriers and facilitators to health care for children with brain cancer and their families., Methods: A qualitative approach was taken using semi-structured interviews. Eligible participants were clinicians of any discipline providing care to children with brain cancer and their families in Australia. Interviews were conducted by telephone and asked about perceived strengths and weaknesses in health care and available resources for this population. Qualitative content analysis used a directed approach with inductive refinement., Results: Eleven clinicians participated, 5 of whom were medical, 3 nursing, and 3 allied health. The overarching theme was that the rarity and diversity of brain tumors in children confers challenges to care that lead to variation in practice. Participants reported having to adapt care from guidelines and patient/family resources designed for adults with brain cancer and children with other cancers, and rely on clinical and research networks. Specialist comprehensive cancer care was generally perceived to offer the best model for accommodating the unique needs of each child/family, but barriers to access were highlighted for children in remote Australia, and long-term follow-up was perceived to be inadequate regardless of where children lived., Significance of Results: Until further brain cancer-specific paediatric guidelines become available, our findings highlight the need for communities of practice to share resources and reduce unwarranted variation., Conclusion: Future research should focus on developing and evaluating guidelines and other resources specific to children with brain cancer, as well as informing suitable models for long-term follow-up care for survivors.

Introduction: This systematic review aims to summarise the available literature on the effect of geriatric assessment (multidimensional health assessment across medical, social, and functional domains; "GA") or comprehensive geriatric assessment (geriatric assessment with intervention or management recommendations; "CGA") compared to usual care for older adults with cancer on care received, treatment completion, adverse treatment effects, survival and health-related quality of life., Materials and Methods: A systematic search of MEDLINE, EMBASE, CINAHL, and PubMed was conducted to identify randomised controlled trials or prospective cohort comparison studies on the effect of GA/CGA on care received, treatment, and cancer outcomes for older adults with cancer., Results: Ten studies were included: seven randomised controlled trials (RCTs), two phase II randomised pilot studies, and one prospective cohort comparison study. All studies included older adults receiving systemic therapy, mostly chemotherapy, for mixed cancer types (eight studies), colorectal cancer (one study), and non-small cell lung cancer (one study). Integrating GA/CGA into oncological care increased treatment completion (three of nine studies), reduced grade 3+ chemotherapy toxicity (two of five studies), and improved quality of life scores (four of five studies). No studies found significant differences in survival between GA/CGA and usual care. GA/CGA incorporated into care decisions prompted less intensive treatment and greater non-oncological interventions, including supportive care strategies., Discussion: GA/CGA integrated into the care of an older adult with cancer has the potential to optimise care decisions, which may lead to reduced treatment toxicity, increased treatment completion, and improved health-related quality of life scores., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Prognostic uncertainty and the need for proxy decision-making owing to cognitive impairment in advanced dementia, adds complexity to end-of-life care planning within the long-term care setting. Case conferences provide a structure to facilitate difficult conversations and an opportunity for family and clinicians to engage in prospective planning, and reach agreement on goals of end-of-life care., Objective: To explore interactions between multidisciplinary healthcare clinicians and families during facilitated case conferences on end-of-life care for residents with advanced dementia., Methods: A qualitative approach was used. Transcripts of audio-recorded case conferences facilitated by a trained registered nurse were coded by two independent researchers and analysed inductively. Transcripts were selected from an available pool until thematic saturation was reached. Emerging themes were confirmed with the wider research group., Results: Thematic saturation was reached after 25 transcripts. An overarching theme concerned the ways in which clinicians and families bridged medical and person-centred perspectives. Subthemes included: details of day-to-day care versus establishing overall goals of care; expression of emotion versus retreat from emotion; and missed opportunities versus expressed cues. Successful facilitation served to 'bridge the gap' between family and clinicians., Conclusion: Facilitation of case conferences for residents with advanced dementia should focus on ensuring that: clinicians do not miss opportunities to discuss end-of-life care; discussions on the minutiae of care regularly return to the resident's broader goals of care; and information on dementia and treatments provided by clinicians is integrated with advice by family members regarding the resident's premorbid values and likely preferences., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Trials of interventions for delirium in various patient populations report disparate outcomes and measures but little is known about those used in palliative care trials. A core outcome set promotes consistency of outcome selection and measurement., Aim: To inform core outcome set development by examining outcomes, their definitions, measures and time-points in published palliative care studies of delirium prevention or treatment delirium interventions., Design: Prospectively registered systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses., Data Sources: We searched six electronic databases (1980-November 2020) for original studies, three for relevant reviews and the International Clinical Trials Registry Platform for unpublished studies and ongoing trials. We included randomised, quasi-randomised and non-randomised intervention studies of pharmacological and non-pharmacological delirium prevention and/or treatment interventions., Results: From 13/3244 studies (2863 adult participants), we identified 9 delirium-specific and 13 non-delirium specific outcome domains within eight Core Outcome Measures in Effectiveness Trials (COMET) taxonomy categories. There were multiple and varied outcomes and time points in each domain. The commonest delirium specific outcome was delirium severity ( n  = 7), commonly using the Memorial Delirium Assessment Scale (6/8 studies, 75%). Four studies reported delirium incidence. Non-delirium specific outcomes included mortality, agitation, adverse events, other symptoms and quality of life., Conclusion: The review identified few delirium interventions with heterogeneity in outcomes, their definition and measurement, highlighting the need for a uniform approach. Findings will inform the next stage to develop consensus for a core outcome set to inform delirium interventional palliative care research.

Background: Access to palliative care in the community enables people to live in their preferred place of care, which is often home. Community palliative care services struggle to provide timely 24-h services to patients and family. This has resulted in calls for 'accessible and flexible' models of care that are 'responsive' to peoples' changing palliative care needs. Digital health technologies provide opportunities to meet these requirements 24-h a day., Aim: To identify digital health technologies that have been evaluated for supporting timely assessment and management of people living at home with palliative care needs and/or their carer(s), and the evidence-base for each., Design: A systematic review of systematic reviews ('meta-review'). Systematic reviews evaluating evidence for virtual models of palliative or end-of-life care using one or more digital health technologies were included. Systematic reviews were evaluated using the Risk of Bias Tool for Systematic Reviews. A narrative approach was used to synthesise results., Data Sources: Medline, Embase, Web of Science, CINAHL and Cochrane Database of systematic reviews were searched for English-language reviews published between 2015 and 2020., Results: The search yielded 2266 articles, of which 12 systematic reviews met criteria. Sixteen reviews were included in total, after four reviews were found via handsearching. Other than scheduled telehealth, video-conferencing, or after-hours telephone support, little evidence was found for digital health technologies used to deliver virtual models of palliative care., Conclusions: There are opportunities to test new models of virtual care, beyond telehealth and/or video conferencing, such as 24-h command centres, and rapid response teams., Systematic Review Registration Number: Prospero CRD42020200266.

Background: A primary brain cancer diagnosis is a distressing, life changing event. It adversely affects the quality of life for the person living with brain cancer and their families ('carers'). Timely access to evidence-based information is critical to enabling people living with brain cancer, and their carers, to self-manage the devastating impacts of this disease., Method: A systematic environmental scan of web-based resources. A depersonalised search for online English-language resources published from 2009 to December 2019 and designed for adults (> 25 years of age), living with primary brain cancer, was undertaken using the Google search engine. The online information was classified according to: 1) the step on the cancer care continuum; 2) self-management domains (PRISMS taxonomy); 3) basic information disclosure (Silberg criteria); 4) independent quality verification (HonCode); 5) reliability of disease and treatment information (DISCERN Sections 1 and 2); and readability (Flesch-Kincaid reading grade)., Results: A total of 119 online resources were identified, most originating in England (n = 49); Australia (n = 27); or the USA (n = 27). The majority of resources related to active treatment (n = 76), without addressing recurrence (n = 3), survivorship (n = 1) or palliative care needs (n = 13). Few online resources directly provided self-management advice for adults living with brain cancer or their carers. Just over a fifth (n = 26, 22%) were underpinned by verifiable evidence. Only one quarter of organisations producing resources were HonCode certified (n = 9, 24%). The median resource reliability as measured by Section 1, DISCERN tool, was 56%. A median of 8.8 years of education was required to understand these online resources., Conclusions: More targeted online information is needed to provide people affected by brain cancer with practical self-management advice. Resources need to better address patient and carer needs related to: rehabilitation, managing behavioural changes, survivorship and living with uncertainty; recurrence; and transition to palliative care. Developing online resources that don't require a high level of literacy and/or cognition are also required.

Purpose: This study aimed to explore medication-related decision-making by health professionals from different disciplines and specialties caring for people with advanced dementia living in long-term care facilities, focusing on dilemmas associated with starting, continuing or deprescribing medications commonly regarded as potentially inappropriate., Methods: Four focus groups were undertaken, each on a different medication type (antibiotics, lipid-lowering agents, opioids and acetylcholinesterase inhibitors). Transcripts underwent qualitative analysis using line by line inductive coding and then a person-centred framework to highlight themes across medication types., Results: Sixteen participants participated in focus groups. Regardless of medication type or dilemma, results suggested decision-making for residents with advanced dementia should begin with discussing goals of care and engaging with families, and be viewed as an iterative process involving regular monitoring and adjustment. Decision-making was seen as requiring a dialectical approach involving multiple perspectives, with an emphasis on establishing communication between health professionals, family and the person with dementia to better understand goals/preferences for care., Conclusion: Inter-professional collaboration enables sharing of clinical experience/expertise, differing disciplinary perspectives and knowledge about the resident. Continuing a medication should be considered an active decision that carries as much responsibility as starting or deprescribing.

Background Medication reviews by pharmacists have been shown to identify and reduce drug-related problems in long-term care residents. Objective To explore pharmacist perspectives of the Australian Government funded pharmacist-conducted residential medication management review and its role improving the quality and safety of prescribing in long-term care, in particular for those living with advanced dementia. Setting Australian Long-term care pharmacists. Method A qualitative research methodology approach using semi-structured interviews was used, with participants pharmacists with Residential Medication Management Review experience. Interviews were recorded, transcribed and coded utilising a meta-model of Physician-Community Pharmacy Collaboration in medication review. Main outcome measure Pharmacists' perspectives on the Residential Medication Management Review and how to improve the quality of reviews for residents with advanced dementia. Results Fifteen accredited pharmacists participated. The majority believed that the Residential Medication Management Review had the potential to improve the quality and safety of medicines but highlighted systemic issues that worked against collaborative practice. Participants emphasised the importance of three-way collaboration between general practitioners, pharmacists and nursing staff and highlighted key strategies for its optimisation. Conclusion Incorporating avenues for greater communication between team members can improve collaboration between health professionals and ultimately the quality of medication reviews.

Exploring various cyclization strategies, using a submicromolar pyrazole HTS screening hit 6 as a starting point, a novel indazole based CCR1 antagonist core was discovered. This report presents the design and SAR of CCR1 indazole and azaindazole antagonists leading to the identification of three development compounds, including 19e that was advanced to early clinical trials., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A HTS screen for CCR1 antagonists afforded a novel sub-micromolar hit 5 containing a pyrazole core. In this report the design, optimization, and SAR of novel CCR1 antagonists based on a pyrazole core motif is presented. Optimization led to the advanced candidate compounds (S)-16q and (S)-16r with 250-fold improved CCR1 potency, excellent off-target selectivity and attractive drug-like properties., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Prescribing medications for nursing home residents with advanced dementia should focus on optimizing function and comfort, reducing unnecessary harms and aligning care goals with a palliative approach., Objective: The aim of the study was to estimate the proportion of Australian nursing home residents with advanced dementia receiving potentially inappropriate medications, and identify those most commonly prescribed and factors associated with their use., Design: Data were collected through retrospective audit of medication charts., Setting/subjects: Two hundred eighteen nursing home residents with advanced dementia from 20 nursing homes participated in a cluster-randomized controlled trial of case conferencing (the IDEAL Study) from June 2013 to December 2014., Measurements: Inappropriate drug use was defined as medications classified as "never appropriate" by the Palliative Excellence in Alzheimer Care Efforts (PEACE) program criteria. Generalized linear mixed models were used to identify variables predicting use of "never" appropriate medications., Results: Over a quarter (n = 65, 30%) of residents received at least one medication classed as "never" appropriate, the most common being lipid-lowering agents (n = 38, 17.4%), antiplatelet agents (n = 18, 8.3%), and acetylcholinesterase inhibitors (n = 16, 7.3%). Residents who had been at the nursing home for ≤10 months (odds ratio [OR] 5.60, 95% confidence interval [CI] 1.74-18.06) and 11-21 months (OR 5.41, 95% CI 1.67-17.75) had significantly greater odds of receiving a never appropriate medication compared with residents who had been at the nursing home for >5 years., Conclusions: Use of potentially inappropriate medications in Australian nursing home residents with advanced dementia is common. A greater understanding of the rationale that underpins prescribing of medications is required.

Introduction: Point-of-care ultrasound (POCUS) is expanding across all medical specialties. As the benefits of US technology are becoming apparent, efforts to integrate US into pre-clinical medical education are growing. Our objective was to describe our process of integrating POCUS as an educational tool into the medical school curriculum and how such efforts are perceived by students., Methods: This was a pilot study to introduce ultrasonography into the Harvard Medical School curriculum to first- and second-year medical students. Didactic and hands-on sessions were introduced to first-year students during gross anatomy and to second-year students in the physical exam course. Student-perceived attitudes, understanding, and knowledge of US, and its applications to learning the physical exam, were measured by a post-assessment survey., Results: All first-year anatomy students (n=176) participated in small group hands-on US sessions. In the second-year physical diagnosis course, 38 students participated in four sessions. All students (91%) agreed or strongly agreed that additional US teaching should be incorporated throughout the four-year medical school curriculum., Conclusion: POCUS can effectively be integrated into the existing medical school curriculum by using didactic and small group hands-on sessions. Medical students perceived US training as valuable in understanding human anatomy and in learning physical exam skills. This innovative program demonstrates US as an additional learning modality. Future goals include expanding on this work to incorporate US education into all four years of medical school., Competing Interests: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The authors disclosed none

Background: Systems for identifying potentially inappropriate medications in older adults are not immediately transferrable to advanced dementia, where the management goal is palliation. The aim of the systematic review was to identify and synthesise published systems and make recommendations for identifying potentially inappropriate prescribing in advanced dementia., Methods: Studies were included if published in a peer-reviewed English language journal and concerned with identifying the appropriateness or otherwise of medications in advanced dementia or dementia and palliative care. The quality of each study was rated using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. Synthesis was narrative due to heterogeneity among designs and measures. Medline (OVID), CINAHL, the Cochrane Database of Systematic Reviews (2005 - August 2014) and AMED were searched in October 2014. Reference lists of relevant reviews and included articles were searched manually., Results: Eight studies were included, all of which were scored a high quality using the STROBE checklist. Five studies used the same system developed by the Palliative Excellence in Alzheimer Care Efforts (PEACE) Program. One study used number of medications as an index, and two studies surveyed health professionals' opinions on appropriateness of specific medications in different clinical scenarios., Conclusions: Future research is needed to develop and validate systems with clinical utility for improving safety and quality of prescribing in advanced dementia. Systems should account for individual clinical context and distinguish between deprescribing and initiation of medications.

Poor solubility and cationic amphiphilic drug-likeness were liabilities identified for a lead series of S1P3-sparing, S1P1 agonists originally developed from a high-throughput screening campaign. This work describes the subsequent optimization of these leads by balancing potency, selectivity, solubility and overall molecular charge. Focused SAR studies revealed favorable structural modifications that, when combined, produced compounds with overall balanced profiles. The low brain exposure observed in rat suggests that these compounds would be best suited for the potential treatment of peripheral autoimmune disorders., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A class of arylsulfonamide glucocorticoid receptor agonists that contains a substituted phenyl group as a steroid A-ring mimetic is reported. The structural design and SAR that provide the functional switching of a GR antagonist to an agonist is described. A combination of specific hydrogen bonding and lipophilic elements on the A-ring moiety is required to achieve potent GR agonist activity. This study culminated in the identification of compound 23 as a potent GR agonist with selectivity over the PR and MR nuclear hormone receptors., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A class of α-methyltryptamine sulfonamide glucocorticoid receptor (GR) modulators was optimized for agonist activity. The design of ligands was aided by molecular modeling, and key function-regulating pharmacophoric points were identified that are critical in achieving the desired agonist effect in cell based assays. Compound 27 was profiled in vitro and in vivo in models of inflammation. Analogs could be rapidly prepared in a parallel approach from aziridine building blocks., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

An uHTS campaign was performed to identify selective inhibitors of PKC-theta. Initial triaging of the hit set based on selectivity and historical analysis led to the identification of 2,4-diamino-5-nitropyrimidines as potent and selective PKC-theta inhibitors. A homology model and initial SAR is presented demonstrating that a 2-arylalkylamino substituent in conjunction with suitable 4-diamino substituent are essential for achieving selectivity over many kinases. Additional hit to lead profiling is presented on selected compounds.

While 1,2-diheteroatom-substituted alkenes represent useful synthetic building blocks, there are no simple, general procedures available for preparation of such compounds. We describe here a simple catalytic procedure based on rhodium C-H bond activation for the synthesis of diheteroatom alkenes of the type R(3)SiOCH=CHG (G = -OR, -NRR').

For most women, pelvic sonography using a transvaginal probe is the imaging modality of choice for evaluating the uterus and adnexae. It is reliable for detecting ovarian cysts and other adnexal masses, and it can often determine if a lesion can be observed on serial examinations or if it requires more urgent attention. Uterine ultrasound is reliable for evaluating both the normal and abnormal endometrium and myometrium. In cases that are technically limited, or in those that are difficult to interpret, a tailored MR imaging examination often can be helpful.

Background: Modifications in plasma amino acid patterns in cirrhotics are attributed to impaired liver function, being more evident in alcoholic than in viral cirrhosis., Aim: To evaluate whether diet influences plasma amino acid concentrations in different aetiological groups of cirrhotics., Patients: Study population comprised 40 patients with cirrhosis (25 virus- and 15 alcohol-related], all Child A, and 30 healthy subjects (controls)., Method: A food frequency and quality questionnaire was utilized to determine dietary history and alcohol intake. Nutritional status was evaluated by anthropometric method. Amino acids were determined, on venous blood samples, using a specific analyzer while cysteine was evaluated by fluorescent high power liquid chromatography, Results: The total daily intake of calories, proteins, lipids, and carbohydrates was similar in all individuals. Food quality distinguished the cirrhotics from the controls, but not the different aetiological groups of cirrhotics. Plasma cysteine levels were significantly lower, while aromatic amino acids and methionine were significantly higher, in all cirrhotics (p<0.001 and p<0.01, respectively, versus controls). The decrease in cysteine and the increase in other amino acids were more marked in alcoholics (p<0.01)., Conclusions: Ethanol intake, but not diet, further enhances the changes in plasma aromatic amino acids, methionine and cysteine induced by impaired liver function in patients with cirrhosis, suggesting a direct interference of alcohol in their metabolism.

Background: Quality of life is an area of increasing interest in hepatology. Studies, so far, have assessed quality of life in patients with chronic virus C-related hepatitis in relation to antiviral therapy by means of generic questionnaires., Aim: To measure quality of life in chronic hepatitis patients without cirrhosis by means of the Nottingham Health Profile questionnaire, a measure of "distress" in comparison with the Medical Outcome Survey SF-36, an index of well-being., Patients: A series of 126 outpatients with chronic hepatitis; 37 on and 89 not on active interferon treatment., Methods: The two questionnaires were used in random order. Clinical and laboratory data were also collected. The final score of any domain of the two questionnaires, for any individual patient, was compared to age-adjusted normal values obtained in 2 random samples of Italian population., Results: Patients showed a significant modification of 3 domains of Nottingham Health Profile (Energy, Social Isolation and Physical Mobility) and 6 domains of SF-36. In relation to interferon treatment, the Nottingham Health Profile questionnaire was able to detect differences in Energy, Physical Mobility and Pain, which were modified only in treated patients. SF-36 did not show any differences in relation to treatment. In addition, the Nottingham Health Profile demonstrated that treated patients had a lower prevalence of concern for family life, possibly due to expectations of treatment itself., Conclusions: Active interferon treatment causes considerable distress in chronic hepatitis C patients, adding to the perceived change in health status caused by liver disease.

Blood from an intraventricular hemorrhage (IVH) can collect in the basilar cisterns and cause ventriculomegaly and eventual need for ventriculoperitoneal (VP) shunt. We looked for sonographic evidence of subarachnoid hemorrhage (SAH) in three basal cisterns and in the Sylvian fissure of 82 infants with IVH, 30 of whom had ventriculomegaly. We found that ultrasonographically diagnosed SAH and measurement of ventricular blood volume predict ventriculomegaly and need for VP shunt.

Alcohol changes the progression of hepatitis C virus (HCV)-related chronic liver disease and may affect the outcome of interferon therapy. The ethanol intake of 245 patients with biopsy-proven chronic hepatitis C with or without cirrhosis, its interaction with laboratory and histological parameters common to alcohol and HCV-mediated liver damage, and its effects on therapy were evaluated. The results show that 60-70% of subjects regularly consumed alcohol (median intake >40 g/day in about 30%). Less than 50% stopped drinking after being diagnosed as having liver disease. Ethanol intake affected: fibrosis, especially in women, HCV RNA levels, which were significantly lower in abstainers than in drinkers (0.6 +/- 0.3 vs 6.9 +/- 5.9 Eq/ml x10(6); P < 0.01), and response to interferon therapy. The number of responders decreased as ethanol intake increased. There were less abstainers than drinkers among non-responders (10.7% vs 63.1% respectively; P < 0.001). Data indicate that alcohol will induce and worsen liver damage and, in subjects with chronic liver disease who continue to drink, adversely affect their response to treatment.

Echolucent images (EL) of cerebral white matter, seen on cranial ultrasonographic scans of very low birth weight newborns, predict motor and cognitive limitations. We tested the hypothesis that markers of maternal and feto-placental infection were associated with risks of both early (diagnosed at a median age of 7 d) and late (median age = 21 d) EL in a multi-center cohort of 1078 infants <1500 x g. Maternal infection was indicated by fever, leukocytosis, and receipt of antibiotic; fetoplacental inflammation was indicated by the presence of fetal vasculitis (i.e. of the placental chorionic plate or the umbilical cord). The effect of membrane inflammation was also assessed. All analyses were performed separately in infants born within 1 h of membrane rupture (n = 537), or after a longer interval (n = 541), to determine whether infection markers have different effects in infants who are unlikely to have experienced ascending amniotic sac infection as a consequence of membrane rupture. Placental membrane inflammation by itself was not associated with risk of EL at any time. The risks of both early and late EL were substantially increased in infants with fetal vasculitis, but the association with early EL was found only in infants born > or =1 after membrane rupture and who had membrane inflammation (adjusted OR not calculable), whereas the association of fetal vasculitis with late EL was seen only in infants born <1 h after membrane rupture (OR = 10.8; p = 0.05). Maternal receipt of antibiotic in the 24 h just before delivery was associated with late EL only if delivery occurred <1 h after membrane rupture (OR = 6.9; p = 0.01). Indicators of maternal infection and of a fetal inflammatory response are strongly and independently associated with EL, particularly late EL.

Background: Ethanol abuse and liver cirrhosis cause a reduction of glutathione blood levels; liver cirrhosis induces an alteration of the plasma amino acid pattern. We evaluated whether or not ethanol abuse affects amino acid levels, particularly those that are involved in metabolizing glutathione in the plasma and erythrocytes of chronic alcohol abusers with or without liver cirrhosis., Methods: We studied 10 chronic alcohol abusers without liver cirrhosis, 10 with alcoholic cirrhosis, 10 affected by hepatitis C virus-related cirrhosis, and 10 healthy subjects. Glutathione, y-glutamyl-cysteine, and cysteine were determined by fluorescent HPLC, glutamic acid, glycine, and other free amino acids by cation exchange chromatography both in the plasma and erythrocytes of all studied subjects., Results and Conclusions: In both alcoholics and cirrhotics, we found a significant increase of plasma-aromatic amino acid and methionine levels, whereas glutathione was significantly reduced. The erythrocytes of these patients showed a significant increase of cysteine, glutamic acid, and glycine; gamma-glutamylcysteine was normal; and glutathione and other free amino acids were significantly decreased. Data suggest that, independent of liver cirrhosis, ethanol abuse affects the metabolism of amino acids and glutathione in both the plasma and the erythrocytes.

Objectives: Because intraventricular hemorrhage (IVH) often precedes the development of sonographically defined white matter damage (WMD) in very preterm infants, we sought to identify the IVH characteristics that predict WMD., Hypotheses: We evaluated variations on the null hypothesis that infants with IVH are no more likely than infants without IVH to have WMD. These variations dealt with characteristics of the IVH (presence or absence of ventriculomegaly) or characteristics of the WMD (size, localization, and laterality)., Methods: A total of 1605 infants weighing 500 to 1500 g at birth between January 1991 and December 1993 underwent standardized cranial ultrasound studies with 6 standard coronal and 5 sagittal views at postnatal days 1 to 3, 7 to 10, and at 3 to 8 weeks., Results: A total of 129 (8%) infants had WMD, either an echodensity alone (n = 59), an echolucency alone (n = 18), or both (n = 52). In analyses that controlled for gestational age, IVH was associated with a fivefold to ninefold increased risk of WMD regardless of size, laterality, or extent of lesions (P

Purpose: To determine the gray-scale and Doppler sonographic features that best enable discrimination between malignant and benign ovarian masses and develop a scoring system for accurate diagnosis with these features., Materials and Methods: Gray-scale and Doppler sonographic features of 211 adnexal masses were correlated with the final diagnosis; the most discriminating features for malignancy were selected with stepwise logistic regression., Results: Twenty-eight masses were malignant and 183 benign. All masses with a markedly hyperechoic solid component or no solid component were benign. For masses with a nonhyperechoic solid component, additional features that allowed statistically significant discrimination of benignity from malignancy were, in decreasing order of importance, (a) location of flow at conventional color Doppler imaging, (b) amount of free intraperitoneal fluid, and (c) presence and thickness of septations. A scoring formula that made use of values based on the logistic regression equation had an area under the receiver operating characteristic curve of 0.98 +/- 0.01. The cutoff score with the highest accuracy had a sensitivity of 93% and specificity of 93%., Conclusion: A solid component is the most statistically significant predictor of a malignant ovarian mass. A multiparameter scoring system that uses three gray-scale and one Doppler feature, developed by means of stepwise logistic regression, has high sensitivity and specificity for predicting malignancy.

Unlabelled: Alpha-gluthathione-S-transferases (alpha-GSTs) are enzymes involved in the cellular detoxifying processes; elevated circulating alpha-GSTs activity is considered to be an early index of liver damage. Glutathione (GSH) is the substrate for alpha-GST action., The Aims of Our Study Were: (1) to evaluate plasma GSH levels and alpha-GST activity in chronic alcohol abusers with or without liver cirrhosis; (2) to define the relationship between these two biochemical parameters; (3) to establish their clinical relevance in patients with alcohol abuse and/or liver damage. We studied 69 subjects (18 healthy subjects and 51 chronic alcohol abusers: 29 without liver cirrhosis and 22 with). Plasma alpha-GST activity was determined on baseline samples and every following day for a total of 10 days in five alcoholics by HEPKIT (Alpha-Biotech, Biotrin International, Dublin, Ireland). GSH was determined on all subjects' baseline samples by fluorescent high-performance liquid chromatography. Alcohol intake was evaluated in all patients by determining blood-alcohol concentrations. Significant increases in plasma alpha-GSTs were observed in 9/29 (31%) alcoholics and 3/22 (13.6%) cirrhotics irrespective of their alcohol intake. GSH was significantly lower than normal values (P < 0.001) in all alcoholics with or without cirrhosis (controls 10.4 +/- 4.8; alcoholics without cirrhosis 3.9 +/- 1.4; alcoholics with cirrhosis 3.3 +/- 1.6). No correlation was observed between plasma alpha-GST and GSH levels. Our data indicate that: (1) alpha-GST activity does not correlate with GSH levels in the plasma; (2) alpha-GSTs do not have clinical relevance as markers of recent alcohol intake; (3) in cirrhotics, alpha-GST does not provide more information than other liver function tests. However, plasma alpha-GST determination may be useful in selecting a subgroup of alcoholics in whom routine biochemical markers of liver damage are within reference ranges.

The aim of this study is to better understand the relationship between placental pathology and risk of intraventricular hemorrhage (IVH). We address two specific hypotheses. 1) Morphologic correlates of pregnancy-induced hypertension (PIH) are associated with a decreased risk of IVH. 2) Morphologic correlates of amniotic sac inflammation (ASI) are associated with an increased risk of IVH. Maternal, neonatal, and placental data were analyzed by univariate and multivariate methods in this prospective cohort study of 1095 very low birth weight infants. A cluster analysis model was used to categorize the placental pathologic features into clusters, the two main ones being PIH and ASI. Deliveries were subdivided by the interval between membrane rupture and delivery as an index of preexisting infection (<1 h) and ascending infection (> or =1 h). Univariate analysis supports both hypotheses. However, in multivariate models that adjusted for such potential confounders as gestational age, labor, and route of delivery, the only associations that persisted were the increased risk of IVH associated with the presence of chorionic or umbilical vasculitis in infants born within 1 h of membrane rupture. Placental correlates of PIH do not provide additional information about IVH risk independent of the presence of other components of the PIH and ASI clusters, and confounders such as gestational age, labor, and route of delivery. Placental correlates of ASI, specifically the fetal responses of chorionic and umbilical vasculitis to preexisting infection, are associated with an increased risk of IVH independent of confounders. Cytokines may provide the link between placental inflammation and fetal/neonatal brain hemorrhage.

There are minimal scientific data describing international caliber off-road cyclists (mountain bikers), particularly as they compare physiologically with international caliber road cyclists. Elite female (N = 10) and male (N = 10) athletes representing the United States National Off-Road Bicycle Association (NORBA) Cross-Country Team were compared with elite female (N = 10) and male (N = 10) athletes representing the United States Cycling Federation (USCF) National Road Team. Submaximal and maximal exercise responses were evaluated during the "championship" phase of the training year when athletes were in peak condition. All physiological tests were conducted at 1860 m. Among the female athletes, physiological responses at lactate threshold (LT) and during maximal exercise (MAX) were similar between NORBA and USCF cyclists with two exceptions: 1) USCF cyclists demonstrated a significantly greater (P < 0.05) absolute (16%) and relative (10%) maximal aerobic power, and 2) MAX heart rate was significantly higher (P < 0.05) for the USCF athletes (6%). Among the male athletes, physiological responses at LT and MAX were similar between NORBA and USCF cyclists with two exceptions: 1) USCF cyclists produced significantly greater (P < 0.05) absolute (18%) and relative (16%) power at LT, and 2) USCF cyclists produced significantly greater (P < 0.05) absolute (12%) and relative (10%) power at MAX. These data suggest that, in general, elite off-road cyclists possess physiological profiles that are similar to elite road cyclists.

Purpose: To determine if the sonographic appearance of solid extratesticular masses enables distinction of benign from malignant disease., Materials and Methods: Sonograms of 19 patients with palpable testicular masses who underwent biopsy were reviewed retrospectively. Appearances of masses on sonograms were correlated with pathologic diagnoses., Results: All masses were well defined and ranged in size from 5.7 to 66.7 mm (mean, 21 mm). On the sonograms, five masses were within the epididymis, and six were distinct from it; seven cases were indeterminate. The epididymis was surgically absent in the remaining patient. Sonographic echogenicity ranged from hypoechoic to hyperechoic relative to that of the testis. At pathologic evaluation, there were 16 (84%) benign and three (16%) malignant lesions. Benign lesions consisted of six adenomatoid tumors, two lipomas, two epidermoid inclusion cysts, two cases of sarcoidosis, and one case each of sperm granuloma, spermatic cord leiomyoma, benign inflammatory nodule, and fibroma. The malignant lesions consisted of scrotal wall liposarcoma, epididymal leiomyosarcoma, and recurrent spindle cell malignancy of the spermatic cord. No sonographic features of masses were useful for distinguishing benign from malignant lesions., Conclusion: The frequency of malignancy (16%) contrasts with prior reports that suggest a very low rate of malignancy among these masses. Sonography is useful for identifying the extratesticular location of a mass but not for distinguishing the nature of the lesion.

Glutathione (GSH) is a principal cellular scavenger of free radicals. Chronic alcohol abuse, as well as liver disease, induces a decrease of hepatic GSH. We evaluated the effect of GSH administration (2.4 g day-1 in saline i.v. for 15 days) on the concentration of GSH in plasma and erythrocytes and on liver function tests, including galactose and antipyrine tests. We studied 40 alcoholic cirrhotic patients: 22 treated with GSH (10 persistent alcohol abusers and 12 weaning from alcohol during the study) and 18 treated with saline only (8 persistent alcohol abusers and 10 abstainers). Treatment with GSH improved the concentration of GSH in plasma and erythrocytes only in abstainers from alcohol; it did not affect liver function tests or galactose clearance. Persistent alcohol consumption significantly prolonged antipyrine metabolism; GSH administration counteracted this effect.

We prospectively studied 96 patients with a history of recurrent spontaneous abortion to determine whether the resistive index of the main uterine artery or subchorionic vessels can allow prediction of pregnancy outcome. The subchorionic RI declined progressively for a mean of 0.54 at 6 weeks to 0.42 at 13 weeks (P < 10(-8), F-test). No significant difference was found in subchorionic RI values between outcomes for liveborn infants versus loss. Uterine artery RI values also declined significantly through the first trimester (P < 10(-8), F-test). Uterine artery RI values tended to be lower in pregnancies ending in loss than in successful gestations; however, there was too much overlap for this index to be clinically useful. In conclusion, first trimester RI does not allow prediction of pregnancy outcome in patients with recurrent abortion.

In order to determine whether the configuration of the normal fetal ductus arteriosus changes with increasing gestational age, we prospectively collected oblique transverse sonographic images of the fetal thorax through the ductus arteriosus. Scans from 240 consecutive normal fetuses with gestational age 20 weeks or more were included in the study. The images were reviewed independently by two sonologists and the ductus arteriosus was graded as: (1) straight; (2) mildly curved (C-shaped, bending < 90 degrees from a straight line); or (3) markedly curved (C-shaped, bending > 90 degrees, or S-shaped). In cases where the two sonologists' gradings did not concur, the images were re-reviewed jointly by both sonologists and a grading was assigned by consensus. Forty-two cases were rejected, due to inadequate images. The ductus arteriosus was graded in 42 fetuses aged 20-25.9 weeks, 48 at 26-31.9 weeks, 74 at 32-37.9 weeks, and 34 at 38 weeks or more for a total of 198 cases. There was a significant trend to greater curvature with increasing gestational age (p < 0.0001). The frequency of a straight ductus arteriosus decreased steadily from 55% of fetuses aged 20-25.9 weeks to 3% of fetuses at 38 weeks or older, while the frequency of marked curvature increased from 2% in the youngest age group to 56% in the oldest. The proportion with mild curvature showed little variation throughout gestation. In summary, the configuration of the ductus arteriosus is variable but tends to become more curved as pregnancy proceeds. Marked curvature or tortuosity of the ductus arteriosus should not be misinterpreted as a great vessel anomaly.

Purpose: To describe the use of vaginal ultrasonography to identify distal ureteral calculi and hydroureter., Materials and Methods: Abdominal and vaginal sonography were performed in 13 women with distal ureteral calculi. Indications for sonography included flank pain, hematuria, and suspected appendicitis. Six patients were pregnant., Results: In each patient, vaginal sonograms demonstrated a distal ureteral calculus; in only two cases was the calculus detected with transabdominal sonography. Distal hydroureter was identified with vaginal scanning in each patient but with abdominal scanning in only two. Hydronephrosis was absent in three patients, mild in six, and moderate in four. Symmetric ureteral jets were noted at transabdominal sonography in two of nine patients. Follow-up transvaginal scans obtained shortly after passage of stones in two patients revealed swelling of the trigone but normal ureteral jets., Conclusion: In symptomatic female patients, use of vaginal sonography should be considered to evaluate the distal ureter for calculi, particularly if the results of transabdominal examination are normal or inconclusive.

Purpose: To determine whether color and pulsed Doppler ultrasound (US) can be used to differentiate benign from malignant ovarian masses., Materials and Methods: Forty-four ovarian masses identified with sonography in 40 patients were confirmed at surgery (n = 35) or followed up to resolution with US (n = 9). Color and pulsed Doppler US were used to calculate the lowest pulsatility index (PI) and resistance index (RI) for each mass., Results: Color Doppler US enabled detection of arterial flow in 24 of 36 benign masses and six of eight malignant masses. PI was lower in malignant masses than in benign masses (P = .002), as was RI (P = .001). Both indexes demonstrated overlap between benign and malignant masses; therefore, no cutoff value for either index had both high sensitivity and high specificity for malignancy: For PI cutoff of 1.0, sensitivity and specificity were 100% and 46%, respectively; for RI cutoff of 0.4, 50% and 96%., Conclusions: While PI and RI tend to be lower in malignant ovarian masses, neither index can be used reliably to differentiate benign from malignant lesions. In addition, lack of detectable flow by means of color Doppler US does not exclude ovarian malignancy.

Sonographic evaluation of the fetal heart is an important part of obstetric sonography. The sonographer and sonologist should be familiar with the sonographic appearance of the normal fetal heart and with common structural abnormalities. Occasionally, normal structures in or adjacent to the fetal heart may simulate an abnormality. Although one should seek consultative sonography in instances of uncertain or questionable findings, unnecessary referral and concern may be avoided in some cases if the sonologist is familiar with normal variants and pitfalls. In this pictorial essay, we present several such pitfalls that we and others have observed in the four-chamber view (Fig. 1) and in views of the ventricular outflow tracts (Figs. 2 and 3).

We reviewed the scrotal sonograms of 31 patients who had a testicular mass consisting of multiple small spherical or tubular anechoic structures in the region of the mediastinum testis. The median age of the patients was 62 years (range, 31-76 years). The abnormality was unilateral in 22 patients and bilateral in nine. Thirty-four (85%) of the 40 involved testicles had coexisting epididymal abnormalities: 32 with epididymal cysts and two with epididymitis. Follow-up sonograms were available in five patients and showed no change up to 4.5 years after the initial diagnosis. Surgical and histologic findings were available in one other patient and showed dilatation of the rete testis. The sonographic appearance and location of the lesions, the frequent presence of an epididymal abnormality, and the surgical and histologic findings in one case suggest that the lesion is due to dilatation of the rete testis, probably associated with obstruction in the epididymis. Recognition of this entity on sonograms may prevent unnecessary orchiectomy.

Obstetric sonograms of 26 fetuses with echogenic material in the gallbladder were reviewed to describe the sonographic findings and clinical significance. Gestational age at the time of diagnosis ranged from 28 to 42 weeks (mean, 36.2 weeks). The echogenic foci were associated with distal shadowing in eight fetuses (30%), comet-tail artifact in nine (35%), and no distal artifact in nine (35%). No hemolytic anemias, other predisposing risk factors, or clinical sequelae associated with biliary tract disease were identified in any of the infants. Postnatal sonographic or pathologic follow-up studies were available in 17 cases. In nine of these 17 infants, the echogenic foci had resolved. In three, the foci have persisted, but none of the children have become symptomatic; the longest period of follow-up with stones still present is 4 1/2 years. Whether all echogenic foci in the fetal gallbladder represent true gallstones remains unknown. Echogenic foci may be seen in the fetal gallbladder during the third trimester. No predisposing fetal risk factors or clinical sequelae were evident in our series. Many echogenic foci, but not all, will resolve.