A cross-sectional study of the relative availability and prominence of shelf space allocated to healthy and unhealthy foods in supermarkets in urban Ireland, by area-level deprivation.

BACKGROUND: Diet-related noncommunicable diseases (NCDs) are a leading cause of ill-health and death across Europe. In Ireland, dietary intakes of saturated fat, free sugar and salt exceed World Health Organization recommendations, and excess consumption follows a social gradient increasing population risk of diet-related NCDs. The retail food environment can influence consumer food choice and subsequent dietary intakes. In high income countries, supermarkets are an increasingly influential actor in consumer food availability, choice, purchase, and subsequent food intake. This study aims to assess the relative availability and prominence of healthy and unhealthy foods in Irish supermarkets, by area-level deprivation. METHODS: This study used a cross-sectional study design, and applied a validated measure, as described in the INFORMAS Protocol: Food Retail - Food availability in supermarkets. Between October 2021 and February 2022, shelf space (m2) (height or depth (cm) × length (cm)) and prominence (visibility), of foods, classified as healthy and unhealthy and represented by a proxy indicator, were collected in supermarkets (n = 36) in County Dublin, Ireland. Overall the proportion of mean relative shelf space (m2), allocated to healthy and unhealthy foods, and its prominence, by area-level deprivation, and retailer, were determined. We used t-tests and one-way ANOVA to analyse possible differences between the proportion of relative shelf space available to healthy and unhealthy foods, and its prominence, by area-level deprivation and retailer. RESULTS: The study found the proportion of shelf space measured allocated to unhealthy food was 68.0% (SD 10.6). Unhealthy foods were more likely to be in areas of high prominence. Overall, there was no statistically significant difference between the proportion of relative shelf space available to unhealthy foods in areas of high and low deprivation. A statistically significant difference in the proportion of relative shelf space allocated to healthy and unhealthy food by area level deprivation was found in one retailer. CONCLUSION: Unhealthy foods had a higher proportion of shelf space and were more prominent than healthy foods in supermarkets in County Dublin, Ireland. The current availability and prominence of foods in supermarkets does not align with Food Based Dietary Guideline recommendations and does not support consumers to make healthier food choices. There is a need for supermarkets in Ireland to improve the availability and prominence of healthy foods to support consumers to make healthier food choices.

A polymorphism in the OPRM1 3'-untranslated region is associated with methadone efficacy in treating opioid dependence.

The µ-opioid receptor (MOR) is the primary target of methadone and buprenorphine. The primary neuronal transcript of the OPRM1 gene, MOR-1, contains a ~13 kb 3' untranslated region with five common haplotypes in European-Americans. We analyzed the effects of these haplotypes on the percentage of opioid positive urine tests in European-Americans (n=582) during a 24-week, randomized, open-label trial of methadone or buprenorphine/naloxone (Suboxone) for the treatment of opioid dependence. A single haplotype, tagged by rs10485058, was significantly associated with patient urinalysis data in the methadone treatment group. Methadone patients with the A/A genotype at rs10485058 were less likely to have opioid-positive urine drug screens than those in the combined A/G and G/G genotypes group (relative risk=0.76, 95% confidence intervals=0.73-0.80, P=0.0064). Genotype at rs10485058 also predicted self-reported relapse rates in an independent population of Australian patients of European descent (n=1215) who were receiving opioid substitution therapy (P=0.003). In silico analysis predicted that miR-95-3p would interact with the G, but not the A allele of rs10485058. Luciferase assays indicated miR-95-3p decreased reporter activity of constructs containing the G, but not the A allele of rs10485058, suggesting a potential mechanism for the observed pharmacogenetic effect. These findings suggest that selection of a medication for opioid dependence based on rs10485058 genotype might improve outcomes in this ethnic group.

Self-rated health literacy is associated with exercise frequency among adults aged 50+ in Ireland.

Background: The aim of this study was to investigate the relationship between self-rated health literacy and self-reported exercise frequency among people aged 50+ in Ireland. Methods: Data were from the European Health Literacy Survey (2011) a nationally representative, cross-sectional survey of adults aged 15+ from eight countries. Health literacy was measured using composite indices (0-50, low to high) in three domains: healthcare, disease prevention and health promotion. Participants reported how often they exercised for 30 min or longer in the month prior to survey. Multivariate logistic regression analysis was used to examine the association between exercise frequency (almost daily activity vs. weekly or less) and health literacy among participants aged 50+ in Ireland (n = 389). All models were fully adjusted for age, gender, employment status, marital status, social status, education, financial deprivation and having a physically limiting illness. Results: An increased odds of exercising almost daily was associated with understanding disease prevention (OR = 1.18, 95% CI 1.03-1.35) and health promotion information (OR = 1.15, 95% CI 1.01-1.32) and accessing (OR = 1.13, 95% CI 1.00-1.29) and evaluating health promotion information (OR = 1.12, 95% CI 1.00-1.26) with ease. Conclusions: Public health approaches to promoting exercise often include providing information about the benefits of regular exercise, promoting affordable options and enhancing the accessibility of the built environment. Public health policy should also consider measures to improve interactive health literacy skills in order to achieve positive behavioural change.

Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing.

Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits and risk for psychopathology.

Recent trends in breast, cervical, and colorectal cancer screening test utilization in Canada, using self-reported data from 2008 and 2012.

In Canada, self-reported data from the Canadian Community Health Survey 2008 and 2012 provide an opportunity to examine overall utilization of breast, cervical, and colorectal cancer screening tests for both programmatic and opportunistic screening. Among women 50-74 years of age, utilization of screening mammography was stable (62.0% in 2008 and 63.0% in 2012). Pap test utilization for women 25-69 years of age remained high and stable across Canada in 2008 and 2012 (78.9% in 2012). The percentage of individuals 50-74 years of age who reporting having at least 1 fecal test within the preceding 2 years increased in 2012 (to 23.0% from 16.9% in 2008), but remains low. Stable rates of screening mammography utilization (about 30%) were reported in 2008 and 2012 among women 40-49 years of age, a group for which population-based screening is not recommended. Although declining over time, cervical cancer screening rates were high for women less than 25 years of age (for whom screening is not recommended). Interestingly, an increased percentage of women 70-74 years of age reported having a Pap test. In 2012, a smaller percentage of women 50-69 years of age reported having no screening test (5.9% vs. 8.5% in 2008), and more women reported having the three types of cancer screening tests (19.0% vs. 13.2%). Efforts to encourage use of screening within the recommended average-risk age groups are needed, and education for stakeholders about the possible harms of screening outside those age groups has to continue.

Enhancing the effectiveness of diabetes self-management education: the diabetes literacy project.

Patient empowerment through self-management education is central to improving the quality of diabetes care and preventing Type 2 Diabetes. Although national programs exist, there is no EU-wide strategy for diabetes self-management education, and patients with limited literacy face barriers to effective self-management. The Diabetes Literacy project, initiated with the support of the European Commission, aims to fill this gap. The project investigates the effectiveness of diabetes self-management education, targeting people with or at risk of Type 2 Diabetes in the 28 EU Member States, as part of a comprehensive EU-wide diabetes strategy. National diabetes strategies in the EU, US, Taiwan, and Israel are compared, and diabetes self-management programs inventorized. The costs of the diabetes care pathway are assessed on a per person basis at national level. A comparison is made of the (cost)-effectiveness of different methods for diabetes self-management support, and the moderating role of health literacy, organization of the health services, and implementation fidelity of education programs are considered. Web-based materials are developed and evaluated by randomized trials to evaluate if interactive internet delivery can enhance self-management support for people with lower levels of health literacy. The 3-year project started in December 2012. Several literature reviews have been produced and protocol development and research design are in the final stages. Primary and secondary data collection and analysis take place in 2014. The results will inform policy decisions on improving the prevention, treatment, and care for persons with diabetes across literacy levels.

The CHRNA5-A3-B4 gene cluster in nicotine addiction.

Nicotine addiction (NA) is a common and devastating disease, such that the annual number of deaths (world-wide) from tobacco-related diseases will double from 5 million in the year 2000 to 10 million in 2020. Nicotine is the only substance in tobacco which animals and humans will self-administer. NA, as a lifetime diagnosis, has been assessed in various approaches, including the concept of cigarettes per day (CPD). Other assessments of NA are somewhat more comprehensive, such as the Fagerstrom Test for Nicotine Dependence or the American Psychiatric Association's Diagnostic and Statistical Manual (fourth edition) diagnosis of nicotine dependence. These different measures have moderate agreement with one another. Twin, family and adoption studies have shown that these different assessments of NA have substantial heritability (that fraction of risk attributable to genetic factors). The heritability of NA has been estimated at 50-75%, depending on the definition and the population under study. DNA-based studies of NA have been somewhat successful in identifying a common haplotype, which increases risk for NA among European-origin populations. This haplotype explains a small amount of variance, accounting for ∼1 CPD, and it includes the α5 and the α3 nicotinic receptor subunit genes (CHRNA5 and CHRNA3). The review will focus on this implicated region. In this risk region, there is a common (among European-origin people) mis-sense single-nucleotide polymorphism in the CHRNA5 gene (D398N), which changes a conserved amino acid from aspartic acid to asparagine. The risk allele (398N) confers decreased calcium permeability and more extensive desensitization, according to in vitro cellular studies, raising the possibility that a positive allosteric modulator of the (α4ß2)(2)α5 type of nicotinic receptor might have therapeutic potential in NA. There are other genetic influences on NA in this region, apart from the mis-sense variant, and additional biological experiments must be done to understand them.

Confirmation of multiple seizure susceptibility QTLs on chromosome 15 in C57BL/6J and DBA/2J inbred mice.

To confirm seizure susceptibility (SZS) quantitative trait loci (QTLs) on chromosome (chr) 15 identified previously using C57BL/6J (B6) and DBA/2J (D2) mice and to refine their genomic map position, we studied a set of three congenic strains in which overlapping segments of chr 15 from D2 were transferred onto the B6 background. We measured thresholds for generalized electroshock seizure (GEST) and maximal electroshock seizure (MEST) in congenic strains and B6-like littermates and also tested their responses to kainic acid (KA) and pentylenetetrazol (PTZ). Results document that MEST is significantly lower in strains 15M and 15D, which harbor medial and distal (telomeric) segments of chr 15 (respectively) from D2, compared with strain 15P, which harbors the proximal (acromeric) segment of chr 15 from D2, and with control littermates. Congenic strains 15P and 15M exhibited greater KA SZS compared with strain 15D and B6-like controls. All congenic strains were similar to controls with regard to PTZ SZS. Taken together, results suggest there are multiple SZS QTLs on chr 15 and that two QTLs harbor gene variants that affect MEST and KA SZS independently. The MEST QTL is refined to a 19 Mb region flanked by rs13482630 and D15Mit159. This interval contains 350 genes, 183 of which reside in areas where the polymorphism rate between B6 and D2 is high. The KA QTL interval spans a 65 Mb region flanked by markers D15Mit13 and rs31271969. It harbors 83 genes in highly polymorphic areas, 310 genes in all. Complete dissection of these loci will lead to identification of genetic variants that influence SZS in mice and provide a better understanding of seizure biology.

Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer.

BACKGROUND: We evaluated the relationship between the detection and prognostic significance of circulating tumor cells (CTCs) and sites of metastases detected by 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: From May 2004 to January 2008, 195 patients with relapsed/progressive MBC underwent whole-body FDG-PET/CT and provided blood samples for assessment of CTC count. RESULTS: Higher CTC numbers were detected in patients with bone metastases relative to those with no bone lesions (mean 65.7 versus 3.3, P = 0.0122) and in patients with multiple bone metastases relative to those with one or two bone lesions (mean 77.7 versus 2.6, P < 0.001). CTCs predicted overall survival (OS) in 108 patients with multiple sites of metastases including bone (P = 0.0008) but not in 58 without bone metastases (P = 0.4111) and in 29 with bone involvement only (P = 0.3552). All 15 patients but one with human epidermal growth factor receptor 2 (HER-2) positive tumors who were treated with trastuzumab-based regimens had <5 CTCs at progression. In multivariate analysis, CTCs, but not bone metastases, remained a significant predictor of OS. CONCLUSION: Presence of extensive bone metastases as detected by FDG-PET/CT is associated with increased CTC numbers in MBC.

Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer.

BACKGROUND: We demonstrated that circulating tumor cell (CTC) number at baseline and follow-up is an independent prognostic factor in metastatic colorectal cancer (mCRC). This analysis was undertaken to explore whether patient and treatment characteristics impact the prognostic value of CTCs. PATIENTS AND METHODS: CTCs were enumerated with immunomagnetic separation from the blood of 430 patients with mCRC at baseline and on therapy. Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of > or = 3 or <3 CTCs/7.5 ml, respectively. Subgroups were analyzed by line of treatment, liver involvement, receipt of oxaliplatin, irinotecan, or bevacizumab, age, and Eastern Cooperative Oncology Group performance status (ECOG PS). RESULTS: Seventy-one percent of deaths have occurred. Median follow-up for living patients is 25.8 months. For all patients, progression-free survival (PFS) and overall survival (OS) for unfavorable compared with favorable baseline CTCs is shorter (4.4 versus 7.8 m, P = 0.004 for PFS; 9.4 versus 20.6 m, P < 0.0001 for OS). In all patient subgroups, unfavorable baseline CTC was associated with inferior OS (P < 0.001). In patients receiving first- or second-line therapy (P = 0.003), irinotecan (P = 0.0001), having liver involvement (P = 0.002), >/=65 years (P = 0.0007), and ECOG PS of zero (P = 0.04), unfavorable baseline CTC was associated with inferior PFS. CONCLUSION: Baseline CTC count is an important prognostic factor within specific subgroups defined by treatment or patient characteristics.

Audit of ultrasound and decision to operate in groin pain of unknown aetiology with ultrasound technique explained.

AIM: To determine the ability of a groin ultrasound service to identify inguinal/femoral hernias in patients with groin pain and equivocal clinical signs, and to evaluate the number of positive cases undergoing surgery. METHODS AND MATERIALS: A retrospective review of 243 examinations performed during the period January 2000 to June 2004 was undertaken. The referral information, as well as details of the examination and subsequent follow-up, were obtained through our hospital/radiological information system. RESULTS: Of 243 patients, 92 (38%) were referrals from general practitioners and 151 (62%) were hospital referrals. The examinations were performed by radiology consultants or specialist registrars, the former accounting for 228 examinations (94%). The age range of the patients was 3 months to 88 years (mean age=48.7), with a male to female ratio of 3.2:1. One hundred and forty-three examinations were negative for hernias. Two of these patients underwent groin explorations and were found to be normal. The rest were discharged and none returned with related complaints. Ninety-four examinations (39%) were positive for hernias, as a result of which 62 patients underwent surgery. Of these, only four were found to be false-positives giving a positive predictive value of 94% in operated patients. Three scans were equivocal, and three were positive for other conditions. CONCLUSION: In patients with equivocal clinical signs, groin ultrasound is a useful tool for identifying hernias, and therefore, aids surgical management.

Monocytic cell type-specific transcriptional induction of collagenase.

Interstitial collagenase (MMP-1), a metalloproteinase produced by resident and inflammatory cells during connective tissue turnover, cleaves type I collagen fibrils. This catalytic event is rate limiting in remodeling of tissues rich in fibrillar collagen such as the skin and lungs. The regulation of collagenase expression is cell-type specific; bacterial LPS and zymosan, a yeast cell wall derivative, are potent inducers of collagenase expression in macrophages, but do not alter fibroblast collagenase expression. Since promoter elements controlling collagenase transcription in monocytic cells have not been previously defined, we sought to delineate responsive cis-acting elements of the collagenase promoter in transiently transfected human (U937) and murine (J774) monocytic cell lines. Deletion constructs containing as little as 72 bp of 5' -flanking sequence of the collagenase promoter were sufficient for LPS- or zymosan-mediated transcriptional induction, whereas phorbol inducibility exhibited an absolute requirement for upstream elements including the polyoma enhancer A-binding protein-3 site (-83 to -91) and TTCA sequence (-102 to -105) in both monocytic cells and fibroblasts. Mutagenesis of the activator protein-1 [AP-1] site at -72 abolished basal promoter activity and LPS/zymosan inducibility, while mutagenesis of an NF-kappaB-like site at -20 to -10 had no effect. Nuclear extracts from LPS- and zymosan-treated cells showed strong AP-1 activity by gel-shift analysis, and supershift analysis showed the AP-1 complexes contained specific members of both the jun and fos gene families. These data indicate that, in contrast to most LPS effects, AP-1, but not nuclear factor-kappaB, mediates LPS induction of collagenase transcription in macrophagelike cells. Furthermore, as compared to regulation by phorbol ester, collagenase induction in monocytic cells by cell wall derivatives of bacteria or yeast is largely independent of upstream promoter sequences.

Amplification in human breast cancer of a gene encoding a c-myc mRNA-binding protein.

The coding region determinant-binding protein (CRD-BP) binds in vitro to c-myc mRNA and is thought to stabilize the mRNA and increase c-Myc protein abundance. The CRD-BP gene has 15 exons and 14 introns, is single-copy, and is located on chromosome 11 in mice and 17 in humans, close to HER-2/neu. The CRD-BP gene is moderately amplified in 12 of 40 human breast cancers; it is highly amplified in 2 others (14.4 and 20 copies). Despite their proximity, CRD-BP and HER-2/neu genes can be amplified independently. Amplification of a gene that might up-regulate c-Myc abundance could accelerate breast cancer.

Oxidative stress induces DNA damage and inhibits the repair of DNA lesions induced by N-acetoxy-2-acetylaminofluorene in human peripheral mononuclear leukocytes.

Human mononuclear leukocytes were exposed to prooxidants such as H2O2, phorbol-12-myristate-13-acetate, and 4-nitroquinoline-N-oxide, and the effects on induction of DNA damage and repair were evaluated. ADP ribosylation was activated by prooxidant exposure and the response was bimodal with peaks of activation occurring at about 30 min and 4-5 h. Other evidence for prooxidant-induced DNA damage was provided by nucleoid sedimentation assays. Unscheduled DNA synthesis (UDS) was only slightly induced by prooxidant exposure which suggested that either the DNA lesions were repaired by a short patch mechanism involving little UDS, or the repair process was inhibited by prooxidant exposures, or some combination of both. This point was clarified by the fact that the repair of DNA lesions induced by N-acetoxy-2-acetylaminofluorene, an inducer of large patch DNA repair, was inhibited in a dose-dependent manner by exposure to H2O2 and the inhibition was dependent on ADP ribosylation. In contrast, the repair of DNA strand breaks induced by prooxidant exposures as identified above were complete within about 8 h and the repair was independent of ADP ribosylation. Both ADP ribosylation and N-acetoxy-2-acetylaminofluorene-induced UDS were shown to be up- and down-regulated by the redox state of human mononuclear leukocytes indicating a unique mechanism of cellular control over DNA repair.

A delta-opioid receptor genetic variant is associated with abstinence prior to and during cocaine dependence treatment.

INTRODUCTION: An intronic polymorphism in the delta-opioid receptor gene (OPRD1) was previously associated with cocaine dependence in African-Americans. However, it is not known if the polymorphism (rs678849) is associated with dependence-related phenotypes within the cocaine dependent population. METHODS: Cocaine and alcohol dependent subjects were randomized to either topiramate or placebo. Abstinence from cocaine use was confirmed by urine drug screens for benzoylecgonine three times per week. Cocaine withdrawal and craving were assessed at randomization using the Cocaine Selective Severity Assessment (CSSA) and Minnesota Cocaine Craving Scale (MCCS), respectively. Subjects were also interviewed using the Addiction Severity Index (ASI). Genotype at rs678849 was determined for 105 African-American subjects and compared to cocaine abstinence, as well as scores for CSSA, MCCS, and ASI. RESULTS: African-American patients with the C/T or T/T genotypes (n=40) were more likely to be abstinent at the first urine drug screen and more likely to be abstinent for the week prior to randomization compared to patients with the C/C genotype (n=65). Subjects carrying the T allele were also more likely to have abstinent weeks over the course of the trial compared to those with the C/C genotype (RR=1.88, 95% CI=1.59-2.22, p=0.0035). No effects of rs678849 genotype on withdrawal, craving, or addiction severity were observed. CONCLUSIONS: A polymorphism in OPRD1 appears to be associated with both cocaine dependence and cocaine use during treatment in African-Americans. Follow-up studies to confirm the effect on cocaine use are warranted.

The effects of altered distances between obstacles on the jump kinematics and apparent joint angulations of large agility dogs.

Canine agility is a rapidly growing sport in the UK. However, there is a paucity of scientific research examining jump kinematics and associated health and welfare implications of the discipline. The aim of this research was to examine differences in jump kinematics and apparent joint angulation of large (>431 mm at the withers) agility dogs (n = 54), when the distance between hurdles was altered (3.6 m, 4 m and 5 m apart) and to determine how level of skill impacted upon jump kinematics. Significant differences were observed for both the take-off (P <0.001) and landing distances (P <0.001) between the 3.6 m, 4 m and 5 m distances. Further differences were observed when level of skill was controlled for; take-off (F[3,55] = 5.686, P = 0.002) and landing (F[3,55] = 7.552, P <0.001) distances differed at the 3.6 m distance, as did the take-off distance at the 4 m hurdle distance (F[3,50] = 6.168, P = 0.001). Take-off and landing speeds differed for hurdle distances (P <0.001) and level of skill (P <0.001). There were significant differences in apparent neck angle during take-off and landing (P <0.001), lumbar spine angles during take-off, bascule and landing (P <0.01), and in shoulder angles during the bascule phase (P <0.05). The results indicate that agility dogs alter their jumping patterns to accommodate the spacing between hurdles, which ultimately may impact long term health and welfare due to altered kinematics.

Lisinopril in the treatment of hypertensive patients with renal impairment.

Lisinopril, a long-acting angiotensin-converting enzyme inhibitor, is excreted unchanged by the kidney. To determine how reduced renal function affects the drug's antihypertensive efficacy and safety, we studied 26 patients with hypertension associated with impaired renal function, having glomerular filtration rates (GFRs) of 60 ml/minute or less. These patients were enrolled in an open trial of 12 weeks' duration. They were given single daily doses of lisinopril, starting with 2.5 mg in patients with a GFR of less than 30 ml/minute, and 5 mg in the other patients. The dose was titrated to a maximum of 40 mg daily according to the blood pressure response. A diuretic was then added if required. Mean sitting and standing blood pressures at four, eight, and 12 weeks of treatment were significantly reduced compared with pretreatment values. The median dose of lisinopril was 10 mg daily (range, 2.5 to 40 mg), and only four patients required the addition of a diuretic. The mean GFR was unchanged during the study (36 +/- 16.4 ml/minute at baseline, 39 +/- 20.8 ml/minute after 12 weeks of treatment). Twenty-five patients completed the study. The one patient withdrew because of nausea and vomiting due to reflux esophagitis, which was probably not drug-related. Another patient had transient angioneurotic edema and continued to receive lisinopril. No clinically significant hematologic or biochemical abnormalities were observed. Sixteen patients continued to receive lisinopril for one year. Blood pressure control and GFR were well maintained throughout. Thus, in a group of patients who are often difficult to treat, lisinopril provided highly effective blood pressure control and was generally well tolerated.

Antihypertensive and renal effects of lisinopril in older patients with hypertension.

The antihypertensive efficacy and safety of lisinopril were assessed in 60 older patients with a mean age of 75 years (range, 65 to 85 years) in a 12-week open study. Mean ( +/- SEM) blood pressure while sitting was reduced from 190/106 +/- 3.3/1.8 mm Hg at entry to 162/89 +/- 3.2/1.6 mm Hg after 12 weeks of treatment (p less than 0.001). There was no significant alteration in heart rate, and postural hypotension did not occur. Mean glomerular filtration rate at entry was 61.6 +/- 3.4 ml/minute and was unchanged after 12 weeks of therapy at 62.2 +/- 3.0 ml/minute. Fourteen patients continued to receive lisinopril for a period of one year. Blood pressure remained controlled throughout and heart rate remained unchanged. There was a significant reduction in mean arterial pressure from 128.8 +/- 1.9 mm Hg to 105.1 +/- 1.5 mm Hg (p less than 0.001). Biochemical parameters remained unaltered. There was a significant increase in renal blood flow (p less than 0.025) and a corresponding reduction in renovascular resistance (p less than 0.001) following long-term therapy with lisinopril. Thus, lisinopril was generally well-tolerated and highly effective in lowering blood pressure in older hypertensive patients, whereas at the same time renal function was not adversely changed.

Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer.

Nineteen breast cancer patients with measurable metastatic disease who were starting an initial or new line of therapy were evaluated for circulating epithelial cells (CECs) a minimum of 4 times over the course of treatment. In 7 of the 10 CEC+ patients, HER-2 expression was detected on the CECs. CECs expressing HER-2 varied among patients and in serial samples from the same patient including a shift from HER-2- to HER-2+ CECs. These results demonstrate that it is possible to quantify receptors essential for rationally designed therapy using CECs and that reliance on the immunophenotype of the primary tumor can be misleading.