CT pulmonary angiography: optimising acute thoracic imaging by fixed-timing contrast medium delivery with a modified breathing instruction.

AIM: To compare the thoracic vascular opacification achieved using the standard bolus-tracking protocol (BTP) with a fixed-timing protocol (FTP) with a modified breathing instruction during computed tomography pulmonary angiography (CTPA) examinations. MATERIALS AND METHODS: A single-centre review of CTPA examinations performed between July 2018 and January 2019 using the BTP or FTP and weight-based contrast dosing of 20 mg iodine/kg body weight/s for 20 seconds at 100 kV tube potential. Radiodensity (in Hounsfield units) was analysed in the right ventricle, main pulmonary artery (MPA), left atrium, left ventricle, and ascending and descending thoracic aorta (DTA). A p-value of <0.05 was considered significant. RESULTS: Of 782 examinations, 88 BTP and 90 FTP examinations were included. Mean attenuation of the MPA was similar in the FTP (396 ± 106 HU) and BTP (362 ± 119 HU; p=0.06); however, good-quality (≥250 HU) MPA opacification was achieved in more FTP examinations (87/90, 96.7%) compared to the BTP (73/88, 82.9%; p=0.002). Mean attenuation of the DTA was better in the FTP (325 ± 72 HU) than the BTP (228 ± 75 HU; p <0.0001), with good-quality opacification (≥250 HU) in 76/90 (84.4%) FTP examinations compared with 36/88 (40.9%) BTP examinations (p <0.001). CONCLUSION: The FTP achieves better opacification of the MPA and DTA compared to the BTP.

Kinetic risk factors of running-related injuries in female recreational runners.

Our objective was to prospectively investigate the association of kinetic variables with running-related injury (RRI) risk. Seventy-four healthy female recreational runners ran on an instrumented treadmill while 3D kinetic and kinematic data were collected. Kinetic outcomes were vertical impact transient, average vertical loading rate, instantaneous vertical loading rate, active peak, vertical impulse, and peak braking force (PBF). Participants followed a 15-week half-marathon training program. Exposure time (hours of running) was calculated from start of program until onset of injury, loss to follow-up, or end of program. After converting kinetic variables from continuous to ordinal variables based on tertiles, Cox proportional hazard models with competing risks were fit for each variable independently, before analysis in a forward stepwise multivariable model. Sixty-five participants were included in the final analysis, with a 33.8% injury rate. PBF was the only kinetic variable that was a significant predictor of RRI. Runners in the highest tertile (PBF < -0.27 BW) were injured at 5.08 times the rate of those in the middle tertile and 7.98 times the rate of those in the lowest tertile. When analyzed in the multivariable model, no kinetic variables made a significant contribution to predicting injury beyond what had already been accounted for by PBF alone. Findings from this study suggest PBF is associated with a significantly higher injury hazard ratio in female recreational runners and should be considered as a target for gait retraining interventions.

Managing thyrotoxicosis in the acute medical setting.

Thyrotoxicosis is common and can present in numerous ways with patients exhibiting a myriad of symptoms and signs. It affects around 1 in 2000 people annually in Europe1. The thyroid gland produces two thyroid hormones - thyroxine (T4) and triiodothyronine (T3). Thyroxine is inactive and is converted by the tissues and organs that need it into tri-iodothyronine. In health, the production of these thyroid hormones is tightly regulated by the secretion of thyroid stimulating hormone (TSH; thyrotropin) from the pituitary gland. The term 'thyrotoxicosis' refers to the clinical manifestations of hyperthyroidism.

Rethinking antithyroid drugs in pregnancy.

Uncontrolled hyperthyroidism in pregnancy poses a risk to both mother and foetus, and the optimal treatment strategy in this setting remains elusive. Instigation of pharmacological therapy or an alternative intervention during pregnancy requires careful consideration, and the evidence that has underpinned our choice of antithyroid drug has not been robust. Recent research developments have prompted us to question our practice, and reconsider our approach to managing this patient group.

Validation of the Knowledge of Genome Sequencing (KOGS) scale in cancer patients.

INTRODUCTION: The Knowledge of Genome Sequencing (KOGS) questionnaire was recently developed to measure knowledge of genomic sequencing (GS), with preliminary psychometric data supporting its reliability and validity. The aim of this study was to test the reliability and validity of the KOGS in a larger sample, and to confirm its utility in a cancer setting. METHODS: The Genetic Cancer Risk in the Young (RisC) study recruits participants with a personal history of cancer, to investigate heritable cancer causes and future cancer risk using germline GS. Participants (n = 261) in a psychosocial substudy of RisC completed a questionnaire after consent to RisC but before GS, including the KOGS, the Intolerance of Uncertainty Scale, the Chew health literacy scale and items assessing demographic and disease variables. Confirmatory factor analysis (CFA), Cronbach alpha and correlational analyses were undertaken. RESULTS: The CFA testing a single-factor model yielded a good model fit, χ2/df = 2.43, comparative fit index (CFI) = 0.97, root mean square error of approximation (RMSEA) = 0.07 and weighted mean root square (WRMR) = 1.03. Factor loadings of all items were above 0.60 and ranged between.66 and.93. The single factor score demonstrated excellent internal consistency (α = 0.82). KOGS scores were significantly associated with health literacy (r = 0.23, p < .001), having a university education [t(258) = -4.53, p < .001] and having a medical or science background [t(259) = -3.52, p < .001] but not with speaking a language other than English at home, time since diagnosis, previous genetic counselling/testing or intolerance of uncertainty. DISCUSSION: This study confirmed a single-factor structure for the KOGS, and its reliability and validity in a cancer population. Associations with measures of health literacy and education were significant and positive as expected, supporting the KOG's construct validity. Previous genetic counselling may not be sufficient to provide specific knowledge of GS.

The Interaction between HIV and Intestinal Helminth Parasites Coinfection with Nutrition among Adults in KwaZulu-Natal, South Africa.

In South Africa few studies have examined the effects of the overlap of HIV and helminth infections on nutritional status. This cross-sectional study investigated the interaction between HIV and intestinal helminths coinfection with nutritional status among KwaZulu-Natal adults. Participants were recruited from a comprehensive primary health care clinic and stratified based on their HIV, stool parasitology, IgE, and IgG4 results into four groups: the uninfected, HIV infected, helminth infected, and HIV-helminth coinfected groups. The nutritional status was assessed using body mass index, 24-hour food recall, micro-, and macronutrient biochemical markers. Univariate and multivariate multinomial probit regression models were used to assess nutritional factors associated with singly and dually infected groups using the uninfected group as a reference category. Biochemically, the HIV-helminth coinfected group was associated with a significantly higher total protein, higher percentage of transferrin saturation, and significantly lower ferritin. There was no significant association between single or dual infections with HIV and helminths with micro- and macronutrient deficiency; however general obesity and low micronutrient intake patterns, which may indicate a general predisposition to micronutrient and protein-energy deficiency, were observed and may need further investigations.

Induction of AT-specific DNA-interstrand crosslinks by bizelesin in genomic and simian virus 40 DNA.

Bizelesin is a bifunctional AT-specific DNA alkylating drug. Our study characterized the ability of bizelesin to induce interstrand crosslinks, a potential lethal lesion. In genomic DNA of BSC-1 cells, bizelesin formed from approx. 0.3 to 6.03+/-0.85 interstrand crosslinks per 106 base pairs, at 5-100 nM drug concentration, respectively, comparable to the number of total adducts previously determined in the same system (J.M. Woynarowski, M.M. McHugh, L.S. Gawron, T.A. Beerman, Biochemistry 34 (1995) 13042-13050). Bizelesin did not induce DNA-protein crosslinks or strand breaks. A model defined target, intracellular simian virus 40 (SV40) DNA, was employed to map at the nucleotide level sites of bizelesin adducts, including potential interstrand crosslinks. Preferential adduct formation was observed at AT tracts which are abundant in the SV40 matrix associated region and the origin of replication. Many sites, including each occurrence of 5'-T(A/T)4A-3', co-mapped on both DNA strands suggesting interstrand crosslinks, although monoadducts were also formed. Bizelesin adducts in naked SV40 DNA were found at similar sites. The localization of bizelesin-induced crosslinks in AT-rich tracts of replication-related regions is consistent with the potent anti-replicative properties of bizelesin. Given the apparent lack of other types of lesions in genomic DNA, interstrand crosslinks localized in AT-rich tracts, and to some extent perhaps also monoadducts, are likely to be lethal effects of bizelesin.

Role of the X-linked gene GPR174 in autoimmune Addison's disease.

CONTEXT: Autoimmune endocrinopathies demonstrate a profound gender bias, but the reasons for this remain obscure. The 1000 genes on the X chromosome are likely to be implicated in this inherent susceptibility; various theories, including skewed X chromosome inactivation and fetal microchimerism, have been proposed. GPR174 is an Xq21 putative purinergic receptor that is widely expressed in lymphoid tissues. A single-nucleotide polymorphism, rs3827440, encoding Ser162Pro, has recently been associated with Graves' disease in Chinese and Polish populations, suggesting a role of this X chromosome gene in autoimmune disease. OBJECTIVE: We investigated the role of rs3827440 in a UK cohort of patients with autoimmune Addison's disease (AAD). Samples from 286 AAD cases and 288 healthy controls were genotyped using TaqMan single-nucleotide polymorphism genotyping assays (C_25954273_10) on the Applied Biosystems 7900HT Fast real-time PCR system. DESIGN: Using a dominant (present/absent) model, the serine-encoding T allele of rs3827440 was present in 189 of 286 AAD patients (66%) compared with 132 of 288 unaffected controls (46%) [P = .010, odds ratio 1.80 (5%-95% confidence interval 1.22-2.67)]. An allele dosage model found a significant excess of the T allele in AAD patients compared with controls [P = .03, odds ratio 1.34 (5%-95% confidence interval 1.07-1.67)]. CONCLUSION: We have demonstrated a significant association of this X chromosome-encoded immunoreceptor with AAD for the first time. This X-linked gene could have a more generalized role in autoimmunity pathogenesis: G protein-coupled receptors are promising drugable targets, and further work to elucidate the functional role of GPR174 is now warranted.

Effects on DNA integrity and apoptosis induction by a novel antitumor sesquiterpene drug, 6-hydroxymethylacylfulvene (HMAF, MGI 114).

6-Hydroxymethylacylfulvene (HMAF, MGI 114) is a new alkylating antitumor sesquiterpenoid with promising and often curative antitumor activity in vivo. This study examined the ability of the drug to damage cellular DNA, induce apoptosis, and affect the cell cycle of CEM human leukemia cells. No bifunctional lesions, interstrand DNA cross-links or DNA-protein cross-links were seen (by alkaline sedimentation and K+/SDS precipitation, respectively) when using up to 50 microM HMAF. The drug possibly formed some monoadducts, as DNA from drug-treated cells impeded primer extension by Taq polymerase, although only partial inhibition was seen even at 200 microM HMAF. HMAF also induced secondary lesions in cellular DNA, single-strand breaks that were detectable (by nucleoid sedimentation and alkaline sucrose gradient analysis) after a 4-hr treatment at HMAF levels as low as 2 microM, comparable to the growth inhibition IC50 value (1.7 microM). A post-treatment incubation of cells in drug-free medium generated substantial amounts of DNA double-stranded fragments of several kbp, suggesting apoptotic fragmentation (>30% of total DNA following treatment with 20 microM HMAF and a 17-hr post-treatment incubation). Chromatin condensation (by ultrastructural analysis) and induction of sub-G1 particles and apoptotic strand breakage (by multiparametric flow cytometry) confirmed induction of apoptosis by HMAF. HMAF preferentially inhibited DNA synthesis (IC50 approximately 2 microM), which is consistent with an S phase block, observed by cell cycle analysis. The pattern of apoptotic DNA fragmentation, inhibition of DNA synthesis, and blockage in the S phase suggests that these events play a role in the antiproliferative activity of HMAF.

Characterisation of the contractile activity of eletriptan at the canine vascular 5-HT1B receptor.

The functional activity of eletriptan ((R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]- 1 H-indole) at the contractile serotonin (5-hydroxytryptamine; 5-HT) '1B-like' receptor in dog isolated saphenous vein and basilar artery was investigated. Eletriptan, like 5-HT and sumatriptan potently contracted saphenous vein (pEC50: 6.3, 6.9 and 6.1, respectively) and basilar artery (pEC50 7.2, 7.5 and 6.8, respectively). The maximum responses evoked by eletriptan was, unlike sumatriptan, significantly lower than that to 5-HT (intrinsic activity saphenous vein: eletriptan 0.57, 5-HT 1.0, sumatriptan 0.85; basilar artery: eletriptan 0.77, 5-HT 0.98, sumatriptan 0.89). Contractions evoked by eletriptan were antagonised by the 5-HT1B/1D receptor antagonist GR125743 (N-[4-methoxy-3-(4-methyl piperazin-1-yl)phenyl]-3-methyl-4-(4-pyridyl)benzamide) with pA2 values of 9.1 in saphenous vein and 9.4 in basilar artery. Affinity estimates (pKA) for 5-HT and sumatriptan determined from receptor alkylation studies in saphenous vein were 6.6 and 6.3, respectively, compared to the apparent equilibrium dissociation constant (pKp) for eletriptan of 6.8. The rank order of relative intrinsic efficacies (epsilon) was 5-HT > sumatriptan > eletriptan. Thus, eletriptan required greater receptor occupancy (4.4-fold) to evoke an equivalent contraction to 5-HT and sumatriptan in dog isolated saphenous vein. These data demonstrate that eletriptan is a potent partial agonist at the canine vascular 5-HT1B receptor.

Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics of [3H]eletriptan binding at human 5-HT1B and 5-HT1D receptors.

The affinity of eletriptan ((R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]-1H-indole) for a range of 5-HT receptors was compared to values obtained for other 5-HT1B/1D receptor agonists known to be effective in the treatment of migraine. Eletriptan, like sumatriptan, zolmitriptan, naratriptan and rizatriptan had highest affinity for the human 5-HT1B, 5-HT1D and putative 5-ht1f receptor. Kinetic studies comparing the binding of [3H]eletriptan and [3H]sumatriptan to the human recombinant 5-HT1B and 5-HT1D receptors expressed in HeLa cells revealed that both radioligands bound with high specificity (>90%) and reached equilibrium within 10-15 min. However, [3H]eletriptan had over 6-fold higher affinity than [3H]sumatriptan at the 5-HT1D receptor (K(D)): 0.92 and 6.58 nM, respectively) and over 3-fold higher affinity than [3H]sumatriptan at the 5-HT1B receptor (K(D): 3.14 and 11.07 nM, respectively). Association and dissociation rates for both radioligands could only be accurately determined at the 5-HT1D receptor and then only at 4 degrees C. At this temperature, [3H]eletriptan had a significantly (P<0.05) faster association rate (K(on) 0.249 min(-1) nM(-1)) than [3H]sumatriptan (K(on) 0.024 min(-1) nM(-1)) and a significantly (P<0.05) slower off-rate (K(off) 0.027 min(-1) compared to 0.037 min(-1) for [3H]sumatriptan). These data indicate that eletriptan is a potent ligand at the human 5-HT1B, 5-HT1D, and 5-ht1f receptors and are consistent with its potent vasoconstrictor activity and use as a drug for the acute treatment of migraine headache.

Muscarinic antagonists in development for disorders of smooth muscle function.

Compounds with high affinity for muscarinic M3 receptors have been used for many years to treat conditions associated with altered smooth muscle tone or contractility such as urinary urge incontinence, irritable bowel syndrome or chronic obstructive airways disease. M3 selective antagonists have the potential for improved toleration when compared with non-selective compounds. Darifenacin has high affinity (pKi 9.12) and selectivity (9 to 74-fold) for the human cloned muscarinic M3 receptor. Consistent with this profile, the compound potently inhibited M3 receptor mediated responses of smooth muscle preparations (guinea pig ileum, trachea and bladder, pA2 8.66 to 9.4) with selectivity over responses mediated through the M1 (pA2 7.9) and M2 receptors (pA2 7.48). Interestingly, darifenacin also exhibited functional tissue selectivity for intestinal smooth muscle over the salivary gland. The M3 over M1 and M2 selectivity of darifenacin was confirmed in a range of animal models. In particular, in the conscious dog darifenacin inhibited intestinal motility at doses lower than those which inhibit gastric acid secretion (M1 response), increase heart rate (M2 response) or inhibit salivary secretion. Clinical studies are ongoing to determine if darifenacin has improved efficacy and or toleration when compared with non-selective agents.

Effect of temperature on the growth response of Salmonella enteritidis inoculated onto the vitelline membranes of fresh eggs.

The growth response of Salmonella Enteritidis (SE) on the vitelline membrane in vitro was studied with the use of a special tube devised specifically for the inoculation of SE onto the vitelline membrane and for the sampling of the yolk near the inoculation site. This latter ability allowed the detection of the movement of SE into the yolk. The growth of SE on the membrane was compared with that of SE inoculated into yolk and albumen in vitro and in ovo in fresh in-shell eggs. The incubation time was 2 days, and the incubation temperatures were 4, 8, 15, 27, and 37 degrees C. Comparison of the results obtained for in vitro growth showed that at 4, 8, and 15 degrees C, SE behaved as if it were in the albumen, with its numbers decreasing over time. At 27 and 37 degrees C, SE grew as if it were in yolk, with a maximum increase of 4.5 log CFU after 2 days at 37 degrees C. In no experiments involving growth on the vitelline membrane did SE appear in the yolk. Comparisons between in vitro and in ovo growth responses of SE in yolk and albumen indicate that SE growth on the membrane parallels that in the in-shell egg.

Profiling of cAMP and cGMP phosphodiesterases in isolated ventricular cardiomyocytes from human hearts: comparison with rat and guinea pig.

AIMS: Phosphodiesterases (PDEs) are key enzymes controlling cAMP and cGMP levels and spatial distribution within cardiomyocytes. Despite the clinical importance of several classes of PDE inhibitor there has not been a complete characterization of the PDE profile within the human cardiomyocyte, and no attempt to assess which species might best be used to model this for drug evaluation in heart disease. MAIN METHODS: Ventricular cardiomyocytes were isolated from failing human hearts of patients with various etiologies of disease, and from rat and guinea pig hearts. Expression of PDE isoforms was determined using RT-PCR. cAMP- and cGMP-PDE hydrolytic activity was determined by scintillation proximity assay, before and after treatment with PDE inhibitors for PDEs 1, 2, 3, 4, 5 and 7. Functional effects of cAMP PDEi were determined on the contraction of single human, rat and guinea pig cardiomyocytes. KEY FINDINGS: The presence and activity of PDE5 were confirmed in ventricular cardiomyocytes from failing and hypertrophied human heart, as well as PDE3, with ventricle-specific results for PDE4 and a surprisingly large contribution from PDE1 for hydrolysis of both cAMP and cGMP. The total PDE activity of human cardiomyocytes, and the profile of inhibition by PDE1, 3, 4, and 5 inhibitors, was modelled well in guinea pig but not rat cardiomyocytes. SIGNIFICANCE: Our results provide the first full characterisation of human cardiomyocyte PDE isoforms, and suggest that guinea pig myocytes provide a better model than rat for PDE levels and activity.

A community-based integrated nutrition research programme to alleviate poverty: baseline survey.

BACKGROUND: The United Nation's Children Fund (UNICEF) has indicated that urban poverty is primarily found in squatter settlements. At present, 13.5% of all South African households live in informal settlements. The main hypothesis for this empirical study was that micromechanisms would not negatively influence food, nutrition and health of residents in an informal settlement in the Vaal Triangle, South Africa. This hypothesis was tested empirically against the UNICEF framework of the immediate, underlying and basic causes of malnutrition. The purpose of this study was to establish a situation analysis of children and women before designing any intervention. OBJECTIVES: The objectives covered in this paper include Phases I and II of the project, namely planning of the project and determining the demographic and health profile of the sample as part of a situation analysis. STUDY DESIGN: This is a community participatory project. After a strategic participatory planning workshop with stakeholders, a plan of operation document, guiding all field undertakings, was drawn up (Phase 1), followed by a cross-sectional baseline survey (Phase II), situation analysis (Phase III), and implementation of community-based intervention studies (Phase IV). Impact measurement will follow in Phase V. METHODS: After the planning meeting and obtaining consent, a pretested, structured demographic and health questionnaire was used to obtain data from 357 randomly selected households in an informal settlement. Data were statistically analysed for means and standard deviations. RESULTS: The findings of the workshop evaluation indicated that 100% of the participants (n = 34) agreed that a need existed for this project, 74% (n = 24) understood the relevance, and 64% (n = 22) realized the importance for sustainable community development. In the baseline survey, 89% of the respondents lived in zinc shacks with two rooms or less (32.2%), three or four rooms (41.5%) or four rooms or more (26.3%). The household size was six people or more (33%), five people (18.5%), four people (21.3%) and three people or less (27.2%). The unemployment rate was 94.2% for respondents and 80.1% for their partners. The majority of households (42.6%) had a monthly income of

Sequence- and region-specificity of oxaliplatin adducts in naked and cellular DNA.

Oxaliplatin is a clinical anticancer drug with a pharmacological profile distinct from that of cisplatin. Our studies compared site- and region-specificity of lesions induced by oxaliplatin and cisplatin in naked and intracellular DNA, respectively. Oxaliplatin adducts in naked Simian virus 40 (SV40 DNA) were mapped by repetitive primer extension. The sites of oxaliplatin adducts were nearly identical to the sites of cisplatin adducts and were focused in G clusters and GNG motifs probably reflecting intrastrand cross-links. Although alkaline agarose electrophoresis of specific SV40 fragments showed that oxaliplatin formed interstrand cross-links, the levels of this lesion type were low. Drug-induced lesions in discrete loci of cellular DNA were assessed by the polymerase chain reaction stop assay in human tumor A2780 cells. Oxaliplatin at 200 microM induced approximately 1300, approximately 1500, approximately 800, and approximately 300 lesions/10(6) bp in the human beta-globin, c-myc, and HPRT genes and in mitochondrial DNA, respectively. Cisplatin formed two to six times more lesions in the same regions. For both drugs, lesion frequencies seem to parallel the density of drug-binding motifs in the nuclear regions, whereas mitochondrial DNA was disproportionately less affected. Despite less potent induction of DNA lesions, oxaliplatin was more cytotoxic than cisplatin against A2780 cells. Because our findings clearly demonstrate that oxaliplatin forms covalent adducts with a similar sequence- and region-specificity to that of cisplatin, other properties of oxaliplatin adducts, factors other than DNA binding, or both determine the unique features of the mechanism of action of oxaliplatin.

Region-specific DNA damage by AT-specific DNA-reactive drugs is predicted by drug binding specificity.

Bizelesin and adozelesin are DNA-reactive antitumor drugs that alkylate adenines at the 3' ends of their preferred binding sites [5'T(A/T)(4)A3'and 5'(A/T)(3)(-4)A3', respectively]. We used these drugs to examine the determinants for region-specific damage of human genomic DNA. The distribution of bizelesin binding motifs in several regions analyzed "in silico" correlated well with the experimentally determined lesions in these regions assessed by quantitative polymerase chain reaction (QPCR) stop assay. In contrast to the typically low motif density, clusters of potential bizelesin binding sites were found in the matrix-associated regions (MAR domains) of the c-myc and apolipoprotein B (apoB) genes. Accordingly, lesions induced by bizelesin in these domains (2.13 and 7.06 lesions kbp(-1) microM(-1), respectively) markedly exceeded lesions in bulk DNA (0.87 lesions kbp(-1) microM(-1)) or in regions with typically low motif density (e.g., 0.75 and 0.87 lesions kbp(-1) microM(-1) in a beta-globin gene and c-myc origin of replication regions, respectively). Consistent with the more frequent, less localized adozelesin motif, actual lesions induced by adozelesin exceeded by severalfold lesions by bizelesin in four selected regions (within the c-myc and HPRT loci). Whereas adozelesin is likely to affect similar regions as bizelesin, adozelesin's more promiscuous binding probably compromises its relative specificity for such targets. In contrast, findings for bizelesin provide for the first time a proof of principle that a small molecular weight drug can preferentially damage specific regions in cellular DNA. Targeting of critical repetitive sequences, such as AT-rich MAR domains, which allow for clustering of drug binding motif, can be the paradigm for region specificity of small molecular weight agents.

The effect of ageing on the response to frusemide in normal subjects.

The effect of IV frusemide was studied in six healthy young (mean age 26.5 years, range 21-33) and six healthy old (mean age 72.8 years, range 66-80) volunteers. A 24-h urine collection before frusemide showed no difference in volume and sodium excretion, although the old excreted less potassium. Creatinine clearance was significantly reduced in the older subjects. After frusemide, 20 mg IV, the pattern of sodium and water excretion over a 5-h period was different in the two groups. The peak effect was greater in the young and occurred within the first 30 min, but was delayed to between 30 and 60 min in the old. Thus in the young the time for 50% of the total sodium and water to be excreted was half that in the old. This delay in sodium and water excretion was related to baseline creatinine clearance. However, the total water, sodium and potassium excreted in the 5 h after frusemide did not differ in the two groups. These results suggest that the renal effects of frusemide are different in healthy elderly subjects as compared to the young. The delayed and reduced peak response is consistent with fewer nephrons in the elderly kidney.

An unusual case of trisomy and triploidy in a chorion villus biopsy.

A case is reported of a 35-year-old woman who underwent a chorion villus biopsy (CVB) at 17 weeks' gestation after intrauterine growth retardation and oligohydramnios were diagnosed by ultrasound scan. Chromosome analysis of the CVB direct preparations showed a 47,XX,+6 karyotype in all cells. The pregnancy was terminated and subsequent analysis of cultured cells from both the CVB and the post-mortem placenta showed three cell lines: 46,XX, 47,XX,+6 and 69,XXX, while fetal skin and muscle were entirely 69,XXX. An explanation is proposed for the origin and distribution of the three cell lines.

The impact of a clinic-based literacy intervention on language development in inner-city preschool children.

OBJECTIVE: To determine the effect of a clinic-based literacy intervention on the language development of preschool children. METHODS: A convenience sample of families presenting to 2 urban pediatric clinics for well-child care met the following criteria: the family was Latino or black and English- or Spanish-speaking; the child was 2 to 5.9 years old, with no neurodevelopmental disability, at a gestational age of 34 weeks or more, and not attending kindergarten. Participants at the first clinic (intervention group) were exposed to a literacy support program, based on Reach Out and Read (ROR), during the previous 3 years. At the second clinic (comparison group), a similar program started 3 months before the study. Parent-child reading activities were measured using the READ Subscale of the StimQ. Language development was measured using the One-Word Expressive and Receptive Picture Vocabulary Tests, and was performed in the child's primary language. RESULTS: A total of 122 study participants (49 interventions and 73 comparisons) met inclusion criteria and completed all measures. Intervention and comparison families were similar for most sociodemographic variables. Intervention families reported reading together with their children approximately 1 more day per week. Intensity of exposure to ROR (measured by total number of contacts with the program) was associated with increased parent-child reading activities, as measured by the StimQ-Read Subscale (r = 0.20). Intervention children had higher receptive language (mean: 94.5 vs 84.8) and expressive language (mean: 84.3 vs 81.6). After adjusting for potential confounders in a multiple regression analysis, intervention status was associated with an 8.6-point increase (95% confidence interval [CI]: 3.3, 14.0) in receptive language (semipartial correlation [SR]coefficient = 0.27), and a 4.3-point increase (95% CI: 0.04, 8.6) in expressive language (SR = 0.17). In a similar multiple regression, each contact with ROR was associated with an adjusted mean 0.4-point increase (95% CI: 0.1, 0.6) in receptive score, and an adjusted mean 0.21-point increase (95% CI: 0. 02, 0.4) in expressive score. CONCLUSIONS: ROR is an important intervention, promoting parental literacy support and enhancing language development in impoverished preschool children. Integration of literacy promoting interventions such as these into routine pediatric health care for underserved populations can be recommended.