Individuals' experiences in genetic counseling and predictive testing for familial amyotrophic lateral sclerosis.

As clinical genetic testing in the amyotrophic lateral sclerosis (ALS) diagnostic setting increases, the identification of at-risk family members has also expanded. No practice guidelines specifically for predictive genetic testing exist, and few studies about the psychological impacts of testing in this subgroup have occurred, limiting the ability to tailor recommendations and counseling in this community. We surveyed asymptomatic individuals at risk for inheriting an ALS-associated gene mutation. The 80-question survey was designed using a combination of validated measures (General Anxiety Disorder; FACToR; Decision Regret Scale) and original items. Ninety participants completed the survey, including those who completed predictive genetic testing (N = 42) and those who did not (N = 48). Gene positive individuals experienced greater negativity, uncertainty, and overall psychological impairment (p = 0.002; p < 0.001; p = 0.001). Individuals who had not undergone testing reported thinking about their risk multiple times per day and experiencing more decisional regret than those who tested (p = 0.006). In terms of decision-making, being prepared for potential clinical drug trials was a more important potential benefit among those who underwent testing (p = 0.026). Participants valuing preparedness for clinical drug trials supports the concept that genetic testing for ALS will increase as research in gene-targeted therapeutics progresses. This study describes factors relevant to the genetic testing decision-making process and adaptation to results from the perspective of at-risk individuals, which can ultimately guide genetic counseling practice in this population.

ABO-immune complex formation and impact on platelet function, red cell structural integrity and haemostasis: an in vitro model of ABO non-identical transfusion.

BACKGROUND: Transfusion of ABO non-identical platelets has been associated with fatal haemolytic reactions, increased red cell transfusion needs and other adverse effects, but the practice of ABO matching in platelet transfusion is controversial. Immune complexes can be formed from the anti-A and/or anti-B antibodies and ABO soluble antigen(s) present in donor and recipient plasma after ABO non-identical transfusions. We hypothesized that these immune complexes affect recipient red cell structural integrity, platelet function and haemostasis. STUDY DESIGN AND METHODS: Haemolysis, platelet function and haemostatic function were assessed before and after incubation of recipient red cells, platelets and whole blood with normal saline controls, ABO-identical plasma controls or in vitro-generated ABO-immune complexes. RESULTS: ABO-immune complexes caused significantly increased haemolysis (P < 0·001), inhibition of platelet function (P = 0·001) and disruption of clot formation kinetics (P < 0·005) in both group A and O recipient samples. CONCLUSIONS: Substantial changes in platelet function, red cell integrity and haemostasis occur after in vitro exposure to immune complexes. These in vitro findings may explain, in part, previously observed associations of ABO non-identical platelet transfusions with adverse effects including increased red cell transfusion needs, organ failure and mortality.

Novel anticoagulants: general overview and practical considerations for dental practitioners.

Currently, 4 novel Direct Oral Anticoagulants (DOACs) were approved by the FDA. This review focuses on these agents and proposes a matrix for the general dentists to assess bleeding risk in dental management of patient on DOACs. The outline covers the pharmacology of DOACs (rivaroxaban, apixaban, edoxaban and dabigatran), bleeding complications, risk associated with discontinuation, monitoring/reversal, and implications for the dental practitioners. A total of 18 randomized controlled trials were identified with mixed results in regards to the risk for bleeding. Considering the pharmacology of DOACs and challenges in monitoring and reversing their effect, the dentist should consider carefully the management of patients on DOACs as it may differ from patients on conventional anticoagulants. Based on the type of dental procedure and the medical risk assessment, several general treatment approaches can be considered: continue DOACs, time dental treatment as late as possible after the last DOACs dose, discontinue DOACs for 24hrs, or discontinue DOACs for 48hrs. Based on the current reported dental literature, limited dental surgery may benefit from the first 2 conservative options. However, this needs to be proven in comparative clinical trials.

Phase II study of gemcitabine, oxaliplatin in combination with panitumumab in KRAS wild-type unresectable or metastatic biliary tract and gallbladder cancer.

BACKGROUND: Current data suggest that platinum-based combination therapy is the standard first-line treatment for biliary tract cancer. EGFR inhibition has proven beneficial across a number of gastrointestinal malignancies; and has shown specific advantages among KRAS wild-type genetic subtypes of colon cancer. We report the combination of panitumumab with gemcitabine (GEM) and oxaliplatin (OX) as first-line therapy for KRAS wild-type biliary tract cancer. METHODS: Patients with histologically confirmed, previously untreated, unresectable or metastatic KRAS wild-type biliary tract or gallbladder adenocarcinoma with ECOG performance status 0-2 were treated with panitumumab 6 mg kg(-1), GEM 1000 mg m(-2) (10 mg m(-2) min(-1)) and OX 85 mg m(-2) on days 1 and 15 of each 28-day cycle. The primary objective was to determine the objective response rate by RECIST criteria v.1.1. Secondary objectives were to evaluate toxicity, progression-free survival (PFS), and overall survival. RESULTS: Thirty-one patients received at least one cycle of treatment across three institutions, 28 had measurable disease. Response rate was 45% and disease control rate was 90%. Median PFS was 10.6 months (95% CI 5-24 months) and median overall survival 20.3 months (95% CI 9-25 months). The most common grade 3/4 adverse events were anaemia 26%, leukopenia 23%, fatigue 23%, neuropathy 16% and rash 10%. CONCLUSIONS: The combination of gemcitabine, oxaliplatin and panitumumab in KRAS wild type metastatic biliary tract cancer showed encouraging efficacy, additional efforts of genetic stratification and targeted therapy is warranted in biliary tract cancer.

Correction of ultrasonic array images to improve reflector sizing and location in inhomogeneous materials using a ray-tracing model.

The use of ultrasonic arrays has increased dramatically within recent years due to their ability to perform multiple types of inspection and to produce images of the structure through post-processing of received signals. Phased arrays offer many advantages over conventional transducers in the inspection of materials that are inhomogeneous with spatially varying anisotropic properties. In this paper, the arrays are focused on austenitic steel welds as a representative inhomogeneous material. The method of ray-tracing through a previously developed model of an inhomogeneous weld is shown, with particular emphasis on the difficulties presented by material inhomogeneity. The delay laws for the structure are computed and are used to perform synthetic focusing at the post-processing stage of signal data acquired by the array. It is demonstrated for a simulated austenitic weld that by taking material inhomogeneity and anisotropy into account, superior reflector location (and hence, superior sizing) results when compared to cases where these are ignored. The image is thus said to have been corrected. Typical images are produced from both analytical data in the frequency domain and data from finite element simulations in the time domain in a variety of wave modes, including cases with mode conversion and reflections.

Regulatory assessment of brand changes in the commercial tobacco product market.

BACKGROUND: Regulatory oversight of tobacco product design has gained momentum in the US and internationally. Appropriate standards for assessing commercial brands and characterising product features must be considered a priority. An area of potential concern is in-market design changes adopted within a single commercial brand over time. METHODS: Internal tobacco industry documents were identified and used to assess internal discussion of product guidelines and practices regarding in-market brand changes. RESULTS: Commercial tobacco products undergo a constant process of revision in-market, beginning at the most basic level of physical product characteristics and components, and including every aspect of design. These revisions commonly exceed guidelines for acceptable product variance adopted within the industry. While consumer and market testing is conducted to ensure that products remain acceptable to users, explicit marketing often may not accompany brand changes. In the absence of such marketing, it should not be assumed that a brand remains unchanged. CONCLUSIONS: For manufacturers, assessment of competitor brands includes identification and analysis of non-routine changes; that is, those changes likely to significantly alter the character of a given brand. Regulators must adopt a similar practice in determining standards for product evaluation in the face of ongoing commercial product revision.

Geographical information systems as a tool for monitoring tobacco industry advertising.

BACKGROUND: Although the use of a geographical information systems (GIS) approach is usually applied to epidemiological disease outbreaks and environmental exposure mapping, it has significant potential as a tobacco control research tool in monitoring point-of-purchase (POP) tobacco advertising. DESIGN: An ecological study design approach was applied so as to primarily evaluate and interpret the spatial density and intensity of POP and tobacco industry advertisements within <300 m to high schools in Greece with the application of GIS methodology combining mapping, photographing and global positioning data. RESULTS: The GIS approach identified 133 POP and 44 billboards within 300 m of the school gates of Heraklion schools. On average 13 POP (range 4-21) and 4.4 billboards (range 1-9) were located per school, and all had at least 1 POP within 20 m of the school gate. On average (SD) 9 (6) tobacco advertisements per POP (range 0-25) were noted, and 80% of them were below child height. The GIS protocol identified that kiosks, that were excepted from the Greek ban on tobacco advertising, in comparison to other POP, were found not only to be closer and visible from the school gates (44.1% vs 10.8%, p<0.001) but were also found to have more external advertisements (8 (5) vs 5 (3), p<0.001). CONCLUSIONS: This study demonstrates the effectiveness of a GIS system in monitoring tobacco industry advertising on a large population-based scale and implies its use as a standardised method for monitoring tobacco industry strategies and tobacco control efforts.

Developing smokeless tobacco products for smokers: an examination of tobacco industry documents.

OBJECTIVE: To investigate whether development of smokeless tobacco products (SLT) is intended to target current smokers. METHODS: This study analysed internal tobacco industry documents to describe research related to the smokeless tobacco market. Relevant documents included those detailing the development and targeting of SLT products with a particular emphasis on moist snuff. RESULTS: Cigarette and SLT manufacturers recognised that shifting demographics of SLT users, as well as indoor smoking restrictions, health concerns and reduced social acceptability of smoking could impact the growth of the SLT market. Manufacturers developed new SLT products to target cigarette smokers promoting dual cigarette and SLT use. CONCLUSIONS: Heavy marketing of new SLT products may encourage dual use and result in unknown public health effects. SLT products have been designed to augment cigarette use and offset regulatory strategies such as clean indoor air laws. In the United States, the SLT strategy may provide cigarette companies with a diversified range of products under the prospect of federal regulation. These products may pose significant challenges to efforts by federal agencies to reduce harm caused by tobacco use.

Free nicotine content and strategic marketing of moist snuff tobacco products in the United States: 2000-2006.

BACKGROUND: From 2000 to 2006, moist snuff sales have increased and now account for 71% of the smokeless tobacco market. Previous research has shown that major manufacturers of smokeless tobacco products manipulated free nicotine, the form most readily absorbed, to promote tolerance and addiction. AIM: This study examines the possibility that company-specific and brand-specific strategies of the major moist snuff manufacturers involve controlling free nicotine content and ease of dosing with products that are designed and targeted to specific groups. This study looks at the current total US moist snuff market with product design data from the Massachusetts Department of Public Health; moist snuff use from the National Survey on Drug Use and Health; market data from ACNielsen; and magazine advertising expenditures from TNS Media Intelligence. RESULTS: (1) The levels of free nicotine of moist snuff products have increased over time for several major manufacturers; (2) the number and variety of sub-brands have increased over time; (3) changes in design, as reflected by variation in free nicotine associated with pH or tobacco leaf, or both, have enhanced the ease and uniformity of dosing; (4) marketing through price and advertising has increased; and (5) youth use has increased. CONCLUSION: A combination of factors including brand proliferation, control of free nicotine and product design has most likely resulted in the expanded consumption of moist snuff, particularly among young people.

Screening for asymptomatic urogenital Chlamydia trachomatis infection at a large Dublin maternity hospital: results of a pilot study.

BACKGROUND: There are currently no Irish guidelines on screening for Chlamydia trachomatis infection in pregnancy. Prevalence rates in the antenatal population are not known which has prevented the development of screening recommendations for this group. AIMS: The objective of this study was to determine the prevalence of asymptomatic urogenital C. trachomatis infection in young women attending for care at a large maternity hospital. METHODS: All patients aged 25 years and under attending the Hospital between December 2011 and December 2013 were offered screening for urogenital C. trachomatis infection. Nucleic acid amplification testing of the C. trachomatis cryptic plasmid was performed on either endocervical swabs or first void urine samples. RESULTS: There were 2687 women tested for C. trachomatis infection, 83.4 % (2241/2687) through the antenatal clinics, 7.1 % (193/2687) through the gynaecology clinic, and 9.4 % (253/2687) through the emergency department. The rate of a positive test result was 5.6 % (151/2687) overall. The rates in women ages 16-18, 19-21 and 22-25 years were 9.1 % (31/340), 6.5 % (50/774) and 4.4 % (69/1561), respectively. A positive test result was more likely in those who were unemployed (p = 0.04), those who were Irish (p = 0.03) and those who were unmarried (p < 0.01). There were no cases of neonatal C. trachomatis infection in babies born to mothers who were screened in early pregnancy. CONCLUSIONS: The prevalence rate of detected C. trachomatis infection was 5.6 % in the study population. Screening of antenatal patients may have a role in preventing vertical transmission of infection to the neonate.

Brand differences of free-base nicotine delivery in cigarette smoke: the view of the tobacco industry documents.

The recent availability of internal tobacco industry documents provides significant insight into industry knowledge and manipulation of tobacco smoke delivery. One critical area of research is the role of smoke chemistry in determining the absorption and effects of smoke constituents, especially harm producing or pharmacologically active compounds. Independent scientific research has suggested that the nicotine dosing characteristics, hence the addiction potential of cigarettes, may be determined in part by the amount of free-base nicotine in cigarette smoke and its effects on the location, route, and speed of absorption in the body and on the sensory perception effects of the inhaled smoke. Tobacco industry documents describe the use of a number of methods internally for measuring free-base nicotine delivery. These include the common use of cigarette "smoke pH" as a means to estimate the fraction of free-base nicotine in the particulate matter (PM) in cigarette smoke, as well as efforts to measure free-base nicotine directly. Although these methods do not provide accurate absolute measures of free-base nicotine in smoke, consistencies observed in the findings across the various manufacturers indicate: (1) real relative differences in the acid/base chemistry of the smoke from different brands of cigarettes; (2) a connection between differences in free-base levels and brand-dependent differences in sensory perception and smoke "impact"; and (3) levels of free-base nicotine that are greater than have typically been publicly discussed by the industry. Furthermore, the results of these methods are generally consistent with those of a recent study from the Centers for Disease Control and Prevention which directly measured the free-base fraction of nicotine across a range of cigarette types. Consideration of the likely fundamental importance of free-base nicotine levels in cigarette smoke, together with the efforts discussed in the tobacco industry documents to measure such levels, indicates that the public health community would benefit from additional research to assess directly the delivery of free-base nicotine in cigarette smoke across brands. This may be especially useful for those products ("light", "ultralight", "reduced carcinogen", etc) that have been promoted, either explicitly or implicitly, as "harm reducing".

Reductions in tobacco smoke pollution and increases in support for smoke-free public places following the implementation of comprehensive smoke-free workplace legislation in the Republic of Ireland: findings from the ITC Ireland/UK Survey.

OBJECTIVE: To evaluate the psychosocial and behavioural impact of the first ever national level comprehensive workplace smoke-free law, implemented in Ireland in March 2004. DESIGN: Quasi-experimental prospective cohort survey: parallel cohort telephone surveys of national representative samples of adult smokers in Ireland (n = 769) and the UK (n = 416), surveyed before the law (December 2003 to January 2004) and 8-9 months after the law (December 2004 to January 2005). MAIN OUTCOME MEASURES: Respondents' reports of smoking in key public venues, support for total bans in those key venues, and behavioural changes due to the law. RESULTS: The Irish law led to dramatic declines in reported smoking in all venues, including workplaces (62% to 14%), restaurants (85% to 3%), and bars/pubs (98% to 5%). Support for total bans among Irish smokers increased in all venues, including workplaces (43% to 67%), restaurants (45% to 77%), and bars/pubs (13% to 46%). Overall, 83% of Irish smokers reported that the smoke-free law was a "good" or "very good" thing. The proportion of Irish homes with smoking bans also increased. Approximately 46% of Irish smokers reported that the law had made them more likely to quit. Among Irish smokers who had quit at post-legislation, 80% reported that the law had helped them quit and 88% reported that the law helped them stay quit. CONCLUSION: The Ireland smoke-free law stands as a positive example of how a population-level policy intervention can achieve its public health goals while achieving a high level of acceptance among smokers. These findings support initiatives in many countries toward implementing smoke-free legislation, particularly those who have ratified the Framework Convention on Tobacco Control, which calls for legislation to reduce tobacco smoke pollution.

Five leading U.S. commercial brands of moist snuff in 1994: assessment of carcinogenic N-nitrosamines.

BACKGROUND: Moist snuff is the only tobacco product in the United States with increasing sales (an increase of 38.4% between 1981 and 1993) and with increased consumption, primarily by male adolescents aged 12-18 years old and young adults aged 19 years old or older. It is known from previous studies that levels of nicotine and the proportion of unprotonated (free) nicotine, as well as the pH, which affects nicotine delivery, vary considerably among the leading snuff brands. Whether concentrations of major carcinogens, such as the nicotine-derived tobacco-specific N-nitrosamines (TSNAs), like N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), also vary among these brands has not been determined previously. PURPOSE: Our purpose was threefold: 1) to determine the concentrations of major carcinogenic nicotine-derived N-nitrosamines in each of the five most popular moist snuff brands; 2) to analyze the quantitative differences in the various snuff components (e.g., NNN) between two major brand categories: a category comprising the brands known to have high levels of unprotonated nicotine (Copenhagen, Skoal fine cut, and Kodiak) versus a category comprising the brands known to have low levels (Hawken and Skoal Bandits); and 3) to compare the differences in the concentrations of nicotine (previously determined), NNN, NNK, and total TSNAs between these two major brand categories. METHODS: Three boxes of each of the five leading U.S. moist snuff brands were bought in July 1994 from retailers in six areas and transferred immediately to the analytical laboratory. After extraction, N-nitrosamino acids and TSNAs were determined on a gas chromatograph interfaced with a thermal energy analyzer (GC-TEA) and integrator. Each 5-g sample of ground, freeze-dried tobacco was extracted twice, and each extract was analyzed twice by GC-TEA. All P values reported are two sided. RESULTS: Copenhagen, Skoal fine cut, and Kodiak as a group had statistically significant higher levels of nicotine (P = .0017), NNN (P < .0001), NNK (P = .0119), and total TSNAs (P < .0001) than the Hawken and Skoal Bandits group. Concentrations (means +/- SD) of nicotine, NNN, NNK, and total TSNAs comparing the two major brand categories are as follows: nicotine--11.6 +/- 1.01 mg/g versus 6.96 +/- 3.62 mg/g (P = .0017), NNN--7.74 +/- 1.70 micrograms/g versus 4.17 +/- 1.35 micrograms/g (P < .0001), NNK--1.23 +/- 0.68 micrograms/g versus 0.61 +/- 0.41 micrograms/g (P = .0119), and total TSNAs--14.3 +/- 3.82 micrograms/g versus 6.3 +/- 2.56 micrograms/g (P < .0001). CONCLUSIONS: The three leading U.S. snuff brands (Copenhagen, Skoal fine cut, and Kodiak; making up 92% of the U.S. market) showed not only high levels of pH, nicotine, and unprotonated (free) nicotine, but also high concentrations of the strongly carcinogenic TSNAs in comparison with the fourth and fifth best selling moist snuff brands, Hawken and Skoal Bandits (3% of the U.S. market).

Fibroblast models of neurological disorders: fluorescence measurement studies.

Biochemical studies of human fibroblasts from patients with neurological disorders have revealed a wealth of information on how such disorders occur. In this review, Gerald Connolly describes how recently developed fluorescence video imaging techniques have been used to study the physiology of skin fibroblasts isolated from patients with certain neurological disorders, including those produced by Alzheimer's disease, Lesch-Nyhan syndrome, mitochondrial disorders, amyotrophic lateral sclerosis and lysosomal disorders. The results of these studies indicate disruptions in cell homeostasis, particularly specific changes in Ca2+ homeostasis and autofluorescence, which mirror changes thought to occur in the CNS of neurologically impaired patients. More extensive studies of these 'systemic changes' using new fluorescent indicators, combined with advances in imaging techniques, are predicted to increase the potential usefulness of human skin fibroblasts as experimental models and to help diagnose and treat neurological disorders.

Uridine and its nucleotides: biological actions, therapeutic potentials.

There are many disorders of pyrimidine metabolism and those that involve an alteration in uridine metabolism have neurological and systemic effects, which provide insights into the biological activity of uridine and its analogues. Studies of the metabolism and actions of pyrimidines have uncovered a wealth of information on how these endogenous metabolites modulate cell physiology. In this article, the roles for the pyrimidine nucleoside uridine and its nucleotide derivatives in the regulation of a number of biological systems are examined and benefits of further studies are outlined. An understanding of how uridine and its nucleotides modulate such vastly complicated biological systems should ultimately lead to the development of new ways for modulating human physiology in both normal and diseased states. Likely targets for therapy include the respiratory, circulatory, reproductive, and nervous systems, and the treatment of cancer and HIV infection.

Cell imaging and morphology: application to studies of inherited purine metabolic disorders.

A number of inherited or drug-induced metabolic disorders involving dysfunctions in purines and pyrimidines are strongly associated with neurological dysfunction, e.g., Lesch Nyhan syndrome. Such disorders have been studied extensively using biochemical and molecular techniques in order to examine how such defects occur, sometimes using in vitro models based upon cultured neuroblastoma cell lines. However, these metabolic dysfunctions may manifest their effects in other ways, such as impaired synaptic transmission and gross abnormalities in neuronal growth and differentiation. This review outlines the latter novel facet of purine research. It is proposed that by employing cell imaging techniques and cultured neuroblastoma cell lines, believed to model the nervous system, significant insights into how inherited disorders of purine metabolism affect neuronal development can be obtained. This review provides an example of the application of these techniques to understand the etiology of Lesch Nyhan syndrome, and encourages further study of the role of purines and pyrimidines in the development of the nervous system.

Toward a comprehensive long term nicotine policy.

Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source.

Effect of the New York State cigarette fire safety standard on ignition propensity, smoke constituents, and the consumer market.

OBJECTIVES: This study examines empirical evidence from the New York experience testing tobacco industry arguments made in opposition to fire safety standards for cigarettes. DESIGN: Percentages of cigarettes exhibiting full length burns (FLBs), cigarette sales before and following the implementation of the New York standards, a sample of retail cigarette prices, brand availability, and selected smoke constituent yields were compared between cigarettes sold in New York and two other states. Cigarette paper analysis was conducted on cigarettes sold in New York. RESULTS: New York cigarette brands averaged 10.0% FLBs as compared to 99.8% for California and Massachusetts brands. Reduced ignition propensity (RIP) appears to have been achieved by cigarette paper banding. Cigarette sales, prices, and brand availability do not appear to have been affected by the New York standards. Yields of the majority of smoke constituents tested did not differ substantially between RIP cigarettes sold in New York as compared to the same brands sold in Massachusetts. Average yields of tar, carbon monoxide, and two compounds were slightly higher, the yields of seven compounds were higher for one brand only, and nicotine was lower, among New York brands tested. CONCLUSIONS: RIP cigarette brands have been designed to meet the New York fire safety standards. Their introduction has not affected cigarette sales or prices in New York. There is no evidence that the small increases in smoke constituent yields affect the already highly toxic nature of cigarette smoke. Data on smoking caused fires, deaths, and injuries dating from after the change in law are not yet available. Such data will be able to address the question of whether the demonstrated reduced ignition standards are associated with reduced fires and injuries. Based on the New York experience, prior industry objections to producing RIP cigarettes are unfounded. Other states and nations should adopt similar standards.

Birth-weight trends in primiparous women in the twentieth century.

We investigated the trend in birth-weights in the Rotunda hospital in primiparous women over the 20th century. There was a significant increase in birth-weight particularly in the latter third of the century. In light of these findings we believe that new approaches to the management of labour in primiparous mothers be developed.

The value of barium enema and colonoscopy in patients infected with HIV.

Double contrast barium enema (DCBE) and colonoscopy were prospectively compared with rigid sigmoidoscopy, rectal biopsy and microbiological examination in the analysis of stool specimens in 58 HIV-1-infected patients with diarrhoea (more than three liquid motions/day for greater than 1 month). In 26 patients no cause for the diarrhoea was found. In 17 patients the cause of diarrhoea was microbiological, and in 19 rectal histology provided a specific diagnosis. In all these patients sigmoidoscopic appearances were abnormal except in those with Cryptosporidium alone. Colonoscopy provided additional information in only one individual, with cytomegalovirus ulcers of the transverse colon. DCBE was abnormal in only seven cases (cytomegalovirus in three, Kaposi's sarcoma in two, Giardia lamblia in two) and in no case provided additional information. A combination of stool microbiology and rectal histology gave a sensitivity of 97% with a positive predictive value of 100%. The sensitivities of DCBE and colonoscopy with histology were low (16 and 62%, respectively) although the specificity for each test was high, with high positive predictive values. We conclude that neither barium enema nor colonoscopy add usefully to rigid sigmoidoscopic biopsy and stool microscopy in HIV-positive patients with diarrhoea.