Complex chronic conditions among children born to women with schizophrenia.

PURPOSE: Maternal schizophrenia is linked to complications in offspring near the time of birth. Whether there is also a higher future risk of the child having a complex chronic condition (CCC) - a pediatric condition affecting any bodily system expected to last at least 12 months that is severe enough to require specialty care and/or a period of hospitalization - is not known. METHODS: In this population-based health administrative data cohort study (Ontario, Canada, 1995-2018), the risk for CCC was compared in 5066 children of women with schizophrenia (the exposed) vs. 2,939,320 unexposed children. Adjusted hazard ratios (aHR) were generated for occurrence of any CCC, by CCC category, and stratified by child sex, and child prematurity. RESULTS: CCC was more frequent in the exposed (7.7 per 1000 person-years [268 children]) than unexposed (4.2 per 100 person-years [124,452 children]) - an aHR of 1.25 (95% CI 1.10-1.41). aHRs were notably higher in 5 of 9 CCC categories: neuromuscular (1.73, 1.28-2.33), cardiovascular (1.94, 1.64-2.29), respiratory (1.83, 1.32-2.54), hematology/immunodeficiency (2.24, 1.24-4.05) and other congenital or genetic defect (1.59, 1.16-2.17). The aHR for CCC was more pronounced among boys (1.32, 1.13-1.55) than girls (1.16, 0.96-1.40), and of similar magnitude in term (1.22, 1.05-1.42) and preterm infants (1.18, 0.95-1.46). CONCLUSIONS: The risk for a CCC appears to be higher in children born to women with schizophrenia. This finding introduces opportunities for targeted preconception counselling, optimization of maternal risk factors, and intervention to support a vulnerable parent population who will experience unique challenges caring for a child with CCCs.

Health care utilisation in infants and young children born to women with intellectual and developmental disabilities: A systematic review and meta-analysis.

BACKGROUND: Mothers with intellectual and developmental disabilities (IDD) experience socio-economic and health disparities which could impact their offspring's health care utilisation. We systematically reviewed evidence on health care utilisation in infants and young children of women with and without IDD. METHODS: MEDLINE, EMBASE, CINAHL, and PsycINFO were searched from inception to October 2019 for studies examining preventive care, immunisations, emergency department visits, and hospitalisations. Data extraction and quality assessment were performed using standardised tools. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were generated using random effects models for outcomes with data available from ≥3 studies. RESULTS: Four articles describing three cohort studies and one cross-sectional study met our criteria. Maternal IDD status was associated with increased neonatal intensive care unit admission rates (pooled OR 2.03; 95% CI 1.31, 3.13). There were no differences in immunisation rates or hospitalisations. CONCLUSIONS: Few studies have examined the impact of maternal IDD status on health care utilisation in their infants and young children. More high-quality studies are needed.

Exposure to maternal depressive symptoms in childhood and adolescent suicide-related thoughts and attempts: mediation by child psychiatric symptoms.

AIMS: The nature of the association between child psychiatric symptoms and adolescent suicide-related thoughts (SRT) and attempts (SA) remains unclear. Our objective was to assess whether child psychiatric symptoms from 6 to 10 years of age mediate the association between exposure to maternal depressive symptoms in childhood and offspring SRT and SA in adolescence. METHODS: A population-based cohort study was constructed by linking all eight cycles from the National Longitudinal Survey of Children and Youth (NLSCY), a nationally representative Canadian panel survey conducted from 1994 to 2009. Self-reported maternal depressive symptoms were measured when offspring were between 0 and 5 years. Maternal-reported child psychiatric symptoms and psychiatric comorbid symptoms were measured from 6 to 10 years, and offspring self-reported SRT and SA were measured between 11 and 19 years. Indirect effects, the effect proportion mediated and their corresponding bootstrapped 95% confidence intervals (CI) were estimated. RESULTS: Hyperactivity and inattention significantly mediated the association between maternal depressive symptoms in childhood and risk of both SRT and SA from 11 to 19 years, where approximately 60% (SRT 95% CI 23-94%; SA 95% CI 27-95%) of this association was explained by hyperactivity and inattention. Psychiatric comorbid symptoms also significantly mediated this relationship and accounted for 50% (95% CI 18-81%) of this association with SA. CONCLUSIONS: Targeting hyperactivity and inattention, and co-occurring psychiatric symptoms in offspring of depressed mothers could reduce risk of SRT, eventual SA and halt progression towards suicide. However, further understanding of comorbid psychiatric symptoms in childhood that most strongly predict adolescent SA is needed.

How HIV affects health and service use for adults with intellectual and developmental disabilities.

OBJECTIVE(S): Although rates of human immunodeficiency virus (HIV) are similar for individuals with and without intellectual and developmental disabilities (IDD), very little is known about the health needs and service use of those with IDD and HIV. Among a population with IDD, we compared the physical and mental health profiles, as well as general and mental health service use for those with and without HIV. DESIGN: Retrospective cohort study in Ontario, Canada using linked administrative health and social service databases. METHODS: The prevalence of physical conditions and mental health disorders, and patterns of service use for any reason and service use for mental health issues were compared among Ontario adults with IDD and HIV (n = 107) and without HIV (n = 63 901) in log-binomial models adjusted for age, sex and neighbourhood income and rurality. RESULTS: Adults with IDD and HIV were more likely than those without HIV to have three types of mental health disorders: non-psychotic disorders [aRR: adjusted rate ratio (aRR): 1.22 (95% confidence interval (CI): 1.01-1.47)], psychotic disorders [aRR: 1.57 (1.09, 2.28)] and substance use disorders [aRR: 3.52 (2.53, 4.91)]. Adults with IDD and HIV were also more likely to have emergency department visits [aRR: 1.68 (1.42, 1.98)] and hospital admissions [aRR: 2.55 (1.74, 3.73)] for any reason, and to have mental health emergency department visits and/or admissions [aRR: 2.82 (1.90, 4.18)]. DISCUSSION: Adults with IDD and HIV have complex health profiles and greater health service use than HIV-negative adults with IDD. These findings call for closer integration of programs delivered by the HIV and disability sectors to optimise the health of this patient population.

Maternal and offspring outcomes in women with intellectual and developmental disabilities: a population-based cohort study.

OBJECTIVE: To compare the risks for adverse maternal and offspring outcomes in women with and without intellectual and developmental disabilities. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. POPULATION: Singleton obstetrical deliveries to 18- to 49-year-old women with and without intellectual and developmental disabilities (n = 3932 in the exposed cohort, n = 382 774 in the unexposed cohort; 2002-2011 fiscal years). METHODS: Women with intellectual and developmental disabilities were identified based on diagnoses in health administrative data or receipt of disability income support. The unexposed cohort comprised women without intellectual and developmental disabilities. Modified Poisson regression was used to compute adjusted relative risks (aRR) and 95% confidence intervals (CI) comparing the two cohorts. MAIN OUTCOME MEASURES: Primary maternal outcomes were: gestational diabetes, gestational hypertension, pre-eclampsia, eclampsia, and venous thromboembolism. Primary offspring outcomes were: preterm birth, small for gestational age, and large for gestational age. RESULTS: The exposed cohort, compared with the unexposed cohort, had increased risks for pre-eclampsia (aRR 1.47, 95% CI 1.11-1.93) and venous thromboembolism (aRR 1.60, 95% CI 1.17-2.19). Their offspring had increased risks for preterm birth (aRR 1.63, 95% CI 1.47-1.80) and small for gestational age (aRR 1.35, 95% CI 1.25-1.45). CONCLUSIONS: These findings suggest that there is a need to address modifiable risk factors for adverse outcomes among women with intellectual and developmental disabilities prior to and during pregnancy. Moreover, there is a need to enhance monitoring for maternal and offspring complications in this population. TWEETABLE ABSTRACT: Large cohort study: intellectual and developmental disabilities predispose women/babies to adverse outcomes.

Identifying women at risk for postpartum anxiety: a prospective population-based study.

OBJECTIVE: To develop a multifactorial model to predict anxiety symptomatology at 8 weeks postpartum. METHOD: In a population-based study, 522 women in a health region near Vancouver, Canada, completed questionnaires at 1, 4, and 8 weeks postpartum. Questionnaires included risk factors measured at 1 week (sociodemographic, biological, pregnancy-related, life stressors, social support, obstetric, and maternal adjustment). Sequential logistic regression was completed to develop a predictive model of anxiety symptomatology at 8 weeks (State-Trait Anxiety Inventory score >40). RESULTS: The prevalence of anxiety symptomatology at 1, 4, and 8 weeks postpartum was 22.6%, 17.2%, and 14.8% respectively. In multivariable models, anxiety symptomatology at 1 week (aOR 2.78, 95% CI: 1.04-7.43), multiparous parity (aOR 3.29, 95% CI: 1.28-8.48), history of psychiatric problems (aOR 3.07, 95% CI: 1.19-7.97), perceived stress (1 SD increase: aOR 4.92, 95% CI: 2.62-9.26), and childcare stress (1 SD increase: aOR 1.63, 95% CI: 1.01-2.64) were independent predictors of anxiety symptomatology at 8 weeks. CONCLUSION: While a significant proportion of women experience anxiety symptomatology following childbirth, multiparous women with a psychiatric history who have high levels of diverse stress are at greatest risk. These key factors may be used to promote early identification and secondary preventive interventions.

Brief report: cervical cancer screening in women with intellectual and developmental disabilities who have had a pregnancy.

BACKGROUND: Women with intellectual and developmental disabilities (IDD) have lower cervical cancer screening rates than women without IDD. Key barriers to screening uptake include physician or caregiver assumptions that screening is unnecessary because women with IDD are not sexually active. Our objective was to compare cervical cancer screening rates in women with and without IDD who had had a pregnancy. METHOD: We conducted a population-based retrospective cohort study using linked Ontario (Canada) health and social services administrative data. We identified 20- to 64-year-old women with (N = 5033) and without (N = 527 437) IDD who had had a pregnancy. We examined the occurrence of cervical cancer screening between April 1, 2007 and March 31, 2010. We compared screening rates in women with and without IDD using logistic regression, controlling for age, region of residence, neighbourhood income quintile and morbidity level. RESULTS: Women with IDD who had had a pregnancy were more likely than those without IDD to be young, to live in the lowest neighbourhood income quintile, to live in rural areas and to have high or very high morbidity. Even after controlling for these factors, women with IDD were less likely than women without IDD to be screened (67.7% vs. 77.0%; adjusted odds ratio 0.61; 95% confidence interval 0.58-0.65). CONCLUSIONS: Even among women who have had a pregnancy and are therefore known to have been sexually active, women with IDD face significant disparities in cervical cancer screening. Strategies to promote equitable uptake of cervical cancer screening for women with IDD need to be implemented.

Maternal, fetal, and placental conditions associated with medically indicated late preterm and early term delivery: a retrospective study.

OBJECTIVE: Our objectives were: (1) to examine the association between maternal, fetal, and placental phenotypes of preterm delivery and medically indicated early delivery of singletons during the late preterm and early term periods; and (2) to identify the specific maternal, fetal, and placental conditions associated with these early deliveries. DESIGN: Retrospective study. SETTING: City of London and Middlesex County, Ontario, Canada. SAMPLE: Singleton live deliveries, at 34-41 weeks of gestation to women in London and Middlesex. METHODS: We obtained data from a city-wide perinatal database (2002-2011; n = 25 699). We used multinomial logistic regression for multivariable analyses. MAIN OUTCOME MEASURE: The outcome was the occurrence of medically indicated late preterm (34-36 weeks of gestation) and early term (37-38 weeks of gestation) delivery, versus delivery at full term (39-41 weeks of gestation). RESULTS: After controlling for confounding factors, all phenotypes were associated with increased odds of medically indicated late preterm and early term delivery. Within the maternal phenotype, chronic maternal medical conditions were associated with increased odds of medically indicated early term delivery (e.g. for gastrointestinal disease, adjusted odds ratio, aOR 1.72, 95% CI 1.47-2.00; for anaemia, aOR 1.40, 95% CI 1.20-1.63), but not late preterm delivery. CONCLUSIONS: The aetiology of medically indicated early delivery close to full term is heterogeneous. Patterns of associations suggest slightly different conditions underlying the late preterm and early term phenotypes, with chronic maternal medical conditions being associated with early term delivery but not with late preterm delivery. These results have implications for the prevention of early delivery as well as the identification of high-risk groups among those born early. TWEETABLE ABSTRACT: The aetiology of medically indicated late preterm and early term delivery is heterogeneous.

Biological determinants of spontaneous late preterm and early term birth: a retrospective cohort study.

OBJECTIVE: Our aim was to examine the association between biological determinants of preterm birth (infection and inflammation, placental ischaemia and other hypoxia, diabetes mellitus, other) and spontaneous late preterm (34-36 weeks) and early term (37-38 weeks) birth. DESIGN: Retrospective cohort study. SETTING: City of London and Middlesex County, Canada. SAMPLE: Singleton live births, delivered at 34-41 weeks to London-Middlesex mothers following spontaneous labour. METHODS: Data were obtained from a city-wide perinatal database on births between 2002 and 2011 (n = 17,678). Multivariable analyses used multinomial logistic regression. MAIN OUTCOME MEASURE: The outcome of interest was the occurrence of late preterm (34-36 weeks) and early term (37-38 weeks) birth, compared with full term birth (39-41 weeks). RESULTS: After controlling for covariates, there were associations between infection and inflammation and late preterm birth (aOR = 2.07, 95% CI 1.65, 2.60); between placental ischaemia and other hypoxia and late preterm (aOR = 2.21, 95% CI 1.88, 2.61) and early term (aOR = 1.25, 95% CI 1.13, 1.39) birth; between diabetes mellitus and late preterm (aOR = 3.89, 95% CI 2.90, 5.21) and early term (aOR = 2.66, 95% CI 2.19, 3.23) birth; and between other biological determinants (polyhydramnios, oligohydramnios) and late preterm (aOR = 2.81, 95% CI 1.70, 4.64) and early term (aOR = 1.89, 95% CI 1.32, 2.70) birth. CONCLUSIONS: Our findings show that delivery following spontaneous labour even close to full term may be a result of pathological processes. Because these biological determinants of preterm birth contribute to an adverse intrauterine environment, they have important implications for fetal and neonatal health.

Macrophages as potential targets for zoledronic acid outside the skeleton-evidence from in vitro and in vivo models.

PURPOSE: Multiple cell types of the tumour microenvironment, including macrophages, contribute to the response to cancer therapy. The anti-resorptive agent zoledronic acid (ZOL) has anti-tumour effects in vitro and in vivo, but it is not known to what extent macrophages are affected by this agent. We have therefore investigated the effects of ZOL on macrophages using a combination of in vitro and in vivo models. METHODS: J774 macrophages were treated with ZOL in vitro, alone and in combination with doxorubicin (DOX), and the levels of apoptosis and necrosis determined. Uptake of zoledronic acid was assessed by detection of unprenylated Rap1a in J774 macrophages in vitro, in peritoneal macrophages and in macrophage populations isolated from subcutaneously implanted breast cancer xenografts following ZOL treatment in vivo. RESULTS: Exposure of J774 macrophages to 5 µM ZOL for 24 h caused a significant increase in the levels of uRap1A, and higher doses/longer exposure induced apoptotic cell death. DOX (10 nM/24 h) and ZOL (10 µM/4 h) given in sequence induced significantly increased levels of apoptotic cell death compared to single agents. Peritoneal macrophages and macrophage populations isolated from breast tumour xenografts had detectable levels of uRap1A 24 h following a single, clinically achievable dose of 100 µg/kg ZOL in vivo. CONCLUSION: We demonstrate that macrophages are sensitive to sequential administration of DOX and ZOL, and that both peritoneal and breast tumour associated macrophages rapidly take up ZOL in vivo. Our data support that macrophages may contribute to the anti-tumour effect of ZOL.

Location matters: osteoblast and osteoclast distribution is modified by the presence and proximity to breast cancer cells in vivo.

Bone metastasis is a common incurable complication of breast cancer affecting around 70% of patients with advanced disease. In order to improve outcomes for these patients, the cellular and molecular mechanisms underlying bone metastasis need to be established. The majority of studies to date have focused on end-stage disease and little is known about the events taking place following initial tumour cell colonisation of bone. Here we report the results of a longitudinal study that provides detailed analysis of the spatial and temporal relationship between bone and cancer cells during progression of bone metastasis. Tumour growth in bone was initiated by intra-cardiac inoculation of MDA-MB-231-GFP breast cancer cells in immunocompromised mice. Differentiating between areas of bone in direct contact with the tumour and areas distal to the cancer cells but within the tumour bearing bone, we performed comprehensive analyses of the number and distribution of osteoclasts and osteoblasts. Tumour colonies were detectable in bone from day 10, while reduced trabecular bone volume was apparent from day 19 onwards. Cancer-induced changes in osteoblast and osteoclast numbers differed substantially depending on whether or not the cells were in direct contact with the tumour. Compared to naïve controls, areas of bone in direct contact with the tumour had significantly reduced osteoblast but increased osteoclast numbers, whereas the reverse was found in distal areas. Our data demonstrate that tumour cells induce substantial changes in the bone microenvironment prior to the appearance of bone lesions, suggesting that early therapeutic intervention may be required to oppose the tumour-induced changes to the microenvironment und thus tumour progression.

A single administration of combination therapy inhibits breast tumour progression in bone and modifies both osteoblasts and osteoclasts.

We have previously shown that repeated sequential administration of doxorubicin, followed 24 h later by zoledronic acid, inhibits tumour growth in models of established breast cancer bone metastasis. As breast cancer patients only receive zoledronic acid every 3-4 weeks, the aim of the current study was to establish the anti-tumour and bone effects of a single administration of doxorubicin/zoledronic acid combination therapy in a bone metastasis model. MDA-MB-231-GFP cells were injected i.c. in 6-week-old nude mice. On day 2, animals received PBS, doxorubicin (2 mg/kg i.v.), zoledronic acid (100 µg/kg s.c.) or doxorubicin followed 24 h later by zoledronic acid. Anti-tumour effects were assessed on days 15/23 by quantification of apoptotic and proliferating cells and changes in expression of genes implicated in apoptosis, proliferation and bone turnover. Bone effects were assessed by µCT analysis, bone histomorphometry and measurement of serum markers. A tumour-free control group was included. Combination treatment reduced bone tumour burden compared to single agent or PBS control and increased levels of tumour cell apoptosis on day 15, but this was no longer detectable on day 23. Animals receiving zoledronic acid had increased bone density, without evidence of tumour-induced lesions. Bone histomorphometry showed that zoledronic acid caused a decrease in osteoblast and osteoclast numbers and an increase in osteoclast size, in both tumour-free and tumour-bearing animals. Our data show that although zoledronic acid modifies the bone microenvironment through effects on both osteoblasts and osteoclasts, this does not result in a significant anti-tumour effect in the absence of doxorubicin.

Anti-tumour effects of bisphosphonates--what have we learned from in vivo models?

Bisphosphonates are extensively used to treat cancer-induced bone disease in a range of solid tumours and multiple myeloma, where they reduce the incidence of skeletal related events and improve patients' quality of life. Recent reports indicate that bisphosphonates may also prevent recurrence of breast cancer at peripheral sites, suggesting that these drugs may have anti-tumour effects outside the skeleton. Anti-tumour effects of several bisphosphonates have been reported in a range of tumour cell types in vitro. These positive results have subsequently been supported by investigations of effects of bisphosphonates on tumour growth in vivo, both in bone and at peripheral sites. A reduction of tumour burden and also in cancer-induced bone disease has been reported following bisphosphonate treatment in several model systems, including breast and prostate cancer, osteosarcoma and multiple myeloma. In addition, bisphosphonates have been shown to significantly reduce growth of human tumour cells (including breast, prostate, lung and mesothelioma) implanted subcutaneously in immunocompromised mice. However, the majority of in vivo studies showing a reduction in bone disease and reduced tumour burden have used high doses and frequent administration of bisphosphonates, and the clinical relevance of these data have therefore been the subject of considerable debate. Bisphosphonates may hold greater promise as anti-tumour agents when used in combination with cytotoxic drugs, and several in vivo studies have reported substantial increased inhibition of tumour growth and improved survival when bisphosphonates have been added to standard chemotherapy regimens. This review will summarise the published data on anti-tumour effects of bisphosphonates from in vivo models, alone and in combination with other anti-cancer agents, and highlight the main lessons learned and future challenges in this field.

Choosing a measure of support need: implications for research and policy.

BACKGROUND: The paradigm surrounding the delivery of care for individuals with intellectual disabilities (ID) is shifting from a deficit-based approach to a support-based approach. However, it is unclear whether measures of support act as a proxy for adaptive functioning. METHODS: A sample of 40 staff or family members of individuals with ID completed the Supports Intensity Scale and the Scales of Independent Behavior-Revised, Short Form. Correlations were used to examine the relationship between these scales. RESULTS: The subscales of the Supports Intensity Scale as well as the overall support needs index were highly correlated with both the Broad Independence W score and the support score (which reflects both maladaptive and adaptive behaviours) of the Scales of Independent Behavior-Revised. CONCLUSIONS: The strong correlations between these two scales confirm previous findings that current measures of support and measures of adaptive behaviour tap into the same underlying construct. These findings have implications for the development, use and interpretation of research and planning tools.

Complications of bone metastases: surgical management.

BACKGROUND: Patients with metastatic disease to the bone present a management challenge. Of the complications encountered in these patients, the predominant types that require surgical intervention are pathologic or impending fractures and neurologic compromise secondary to cord compression from spinal metastases. A multimodality approach is helpful in caring for these patients, and addressing complications related to bony metastatic disease with timely and appropriate intervention is an important step in optimizing care and quality of life. METHODS: This article incorporates information from multiple sources and presents recent reviews of the experience at the Memorial Sloan-Kettering Cancer Center with acetabular reconstruction for metastatic lesions, and with the use of the posterolateral transpedicular approach to address metastatic disease in the spine. RESULTS: Of 55 patients who underwent reconstruction of the acetabulum for metastatic disease, although there was a 25% incidence of local disease progression, there was only a 9% incidence of late fixation failure. Of the 41 who were evaluable at 3 months, 83% continued to experience significant pain relief, and 50% of nonambulatory patients regained walking ability secondary to the procedure. Of the patients with more than 2 years of follow-up, 86% maintained pain relief and 71% maintained their ability to ambulate and function in their community. The preliminary series of 25 patients managed with a posterolateral transpedicular approach to address metastatic disease in the spine showed excellent tumor control, pain relief, and neurologic preservation with the technique. Particular benefit was obtained for patients with extensive epidural disease in which an anterior approach was contraindicated. CONCLUSIONS: Although a multimodality approach to the treatment of patients with metastatic disease to bone combining appropriate surgical intervention with systemic therapy and radiation can entail a major operative procedure, the overall benefits to a patient's quality of life outweigh the risks in most cases. Clinician awareness of the various therapeutic options and their indications, and aggressive advocacy of quality of life for these patients, can improve the care delivered to people with metastatic disease.

14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening.

BACKGROUND: The Edinburgh randomised trial of breast-cancer screening recruited women aged 45-64 years from 1978 to 1981 (cohort 1), and those aged 45-49 years during 1982-85 (cohorts 2 and 3). Results based on 14 years of follow-up and 270,000 woman-years of observation are reported. METHODS: Breast-cancer mortality rates in the intervention group (28,628 women offered screening) were compared with those in the control group (26,026) with adjustment for socioeconomic status (SES) of general medical practices. Rate ratios were derived by means of logistic regression for the total trial population and for women first offered screening while younger than 50 years. Analyses were by intention to treat. FINDINGS: Initial unadjusted results showed a difference of just 13% in breast-cancer mortality rates between the intervention and control groups (156 deaths [5.18 per 10,000] vs 167 [6.04 per 10,000]; rate ratio 0.87 [95% CI 0.70-1.06]), but the results were influenced by differences in SES by trial group. After adjustment for SES, the rate ratio was 0.79 (95% CI 0.60-1.02). When deaths after diagnosis more than 3 years after the end of the study were censored the rate ratio became 0.71 (0.53-0.95). There was no evidence of heterogeneity by age at entry and no evidence that younger entrants had smaller or delayed benefit (rate ratio 0.70 [0.41-1.20]). No breast-cancer mortality benefit was observed for women whose breast cancers were diagnosed when they were younger than 50 years. Other-cause mortality rates did not differ by trial group when adjusted for SES. INTERPRETATION: Our findings confirm results from randomised trials in Sweden and the USA that screening for breast cancer lowers breast-cancer mortality. Similar results are reported by the UK geographical comparison, UK Trial of Early Detection of Breast Cancer. The results for younger women suggest benefit from introduction of screening before 50 years of age.

Factors affecting outcome of patients with impalpable breast cancer detected by breast screening.

Factors affecting completeness of excision and outcome, whether conservation or mastectomy, in 152 patients with localized impalpable breast cancer undergoing therapeutic needle-guided wide local excision were assessed by univariate and multivariate analyses using multiple logistic regression. Independent factors related to completeness of excision at the first operation were operator experience (P = 0.0001), and size of the lesion (P = 0.005). Factors related to outcome were operator experience (P = 0.0003), more experienced operators having a higher rate of breast conservation, and tumour size (P = 0.0001), larger lesions being more likely to be treated by mastectomy. Patients initially operated on by the two most experienced surgeons were more than four times less likely to undergo mastectomy than those whose initial wide local excision was performed by a less experienced surgeon.

Neuroradiologic MR applications with multiparametric color composite display.

The purpose of this article is to demonstrate the application of a PC-based multiparameter full color composite display technique of MR images of 14 selected patients with neuropathology while assessing the ability of this technique to display clinically important neuroanatomic and neuropathologic tissues. Using a PC with a 386 microprocessor and full color 24-bit graphics display capabilities, custom and commercially available image-processing softwares were applied to spatially aligned multiparameter proton density, T1-weighted (with and/or without gadolinium-DTPA) and T2-weighted MR image sets obtained from 14 patients with known neuropathology to generate intensity-based color composites. Quantitative color channel applications were used to assess the ability of this technique to differentiate anatomically and pathologically confirmed tissue types into unique color regions within the full color spectrum display in each patient case. Based on the results of pathologic correlation and quantitative color imaging analysis, the application of full color composite generation techniques to multiple MR images of selected neuropathology cases represents a viable technique for displaying diagnostically relevant tissue contrast information in one color image. With this technique, it is possible to generate composites that simultaneously display uniquely color-coded neuroanatomic and neuropathologic tissue information within the context of partially natural-appearing images.

In vivo distribution and cytopathology of variants of human immunodeficiency virus type 1 showing restricted sequence variability in the V3 loop.

The distribution, cell tropism, and cytopathology in vivo of human immunodeficiency virus (HIV) was investigated in postmortem tissue samples from a series of HIV-infected individuals who died either of complications associated with AIDS or for unrelated reasons while they were asymptomatic. Proviral sequences were detected at a high copy number in lymphoid tissue of both presymptomatic patients and patients with AIDS, whereas significant infection of nonlymphoid tissue such as that from brains, spinal cords, and lungs were confined to those with AIDS. V3 loop sequences from both groups showed highly restricted sequence variability and a low overall positive charge of the encoded amino acid sequence compared with those of standard laboratory isolates of HIV type 1 (HIV-1). The low charge and the restriction in sequence variability were comparable to those observed with isolates showing a non-syncytium-inducing (NSI) and macrophage-tropic phenotype in vitro. All patients were either exclusively infected (six of seven cases) or predominantly infected (one case) with variants with a predicted NSI/macrophage-tropic phenotype, irrespective of the degree of disease progression. p24 antigen was detected by immunocytochemical staining of paraffin-fixed sections in the germinal centers within lymphoid tissue, although little or no antigen was found in areas of lymph node or spleen containing T lymphocytes from either presymptomatic patients or patients with AIDS. The predominant p24 antigen-expressing cells in the lungs and brains of the patients with AIDS were macrophages and microglia (in brains), frequently forming multinucleated giant cells (syncytia) even though the V3 loop sequences of these variants resembled those of NSI isolates in vitro. These studies indicate that lack of syncytium-forming ability in established T-cell lines does not necessarily predict syncytium-forming ability in primary target cells in vivo. Furthermore, variants of HIV with V3 sequences characteristic of NSI/macrophage-tropic isolates form the predominant population in a range of lymphoid and nonlymphoid tissues in vivo, even in patients with AIDS.