Workshop report. Health risks of drinking water chlorination by-products: report of an expert working group.

Studies of water chlorination by-products have suggested a possible increased risk of bladder and colon cancers, as well as adverse reproductive and developmental effects such as increased spontaneous abortion rates and fetal anomalies. A workshop for an expert working group was convened to advise Health Canada on the need for further action. Participants were given background papers and a set of key questions to review prior to the meeting. At the workshop, experts presented an overview of what was known to date on water chlorination by-products from toxicologic studies, epidemiologic studies of cancer and adverse reproductive/developmental effects, and risk assessment. This paper summarizes the information provided in the background papers and presentations, describes the consensus arrived at regarding assessment of evidence for level of risk and presents a number of suggestions for future research.

Gifted children with learning disabilities: a review of the issues.

Many people have difficulty comprehending that a child can be gifted and also have learning disabilities. As a result, children with special needs that result from both their high abilities and their learning problems are rarely identified and are often poorly served. This article explores the current policies and practices with regard to defining, identifying, and educating this population. Recommendations are included that would help ensure that students who are gifted and have learning disabilities receive the intervention needed to help them achieve their full potential.

Evaluation of a workshop on Public Education Messages for Reducing Health Risks from Ultraviolet Radiation.

The objective of this paper is to assess the impact of the 1994 Workshop on Public Education Messages for Reducing Health Risks from Ultraviolet Radiation (UVR). The target audience was any organization in Canada doing education on the health risks of UVR. A mailed survey with telephone follow-up was distributed to 130 addresses, including workshop participants, recipients of the workshop report and 40 local public health units. The response rate was 62%. Public health messages from the workshop served as an added impetus or helped to initiate activities around UVR in approximately 40% of organizations over the two years since the workshop. The public health messages were used directly in programming by approximately 38% of all organizations responding. However, looking at those who had previously seen the messages, 61% used them directly in programming. Forty percent of those sampled had never seen a copy of the messages. The results suggest the need for improved dissemination of consensus statements.

Temporal expression of c-fos mRNA following balloon injury in the rat common carotid artery.

OBJECTIVE: Restenosis is a common problem which limits the effectiveness of percutaneous transluminal coronary angioplasty (PTCA). The cellular mechanisms of restenosis appear to involve smooth muscle cell (SMC) migration to the neointima in response to mitogens and growth factors, resulting in proliferation and deposition of cells in the lumen of the vessel. An antibody directed against PDGF attenuates this response in the rat. Thus, signaling cascades induced by growth factors including PDGF may be important targets for therapeutic intervention. METHODS: Since a number of growth factors activate c-fos via the p21-ras signaling pathway, we examined c-fos expression in a time course experiment involving restenotic lesions in rat carotid arteries. Sections of arteries collected at 1, 3, 7, 14 and 28 days following balloon injury were hybridized using a fluorescein-labeled RNA probe to c-fos. Immunohistochemistry was performed with antibodies to proliferating cell nuclear antigen (PCNA) and alpha-smc actin to characterize cellular constituents of the neointima, and detect any correlation between fos expression and PCNA localization. RESULTS: Expression of c-fos was low at day 1. By day 3, the media and adventitia were positively stained. At days 7 and 14, most cells in the neointima were labeled. By day 28, c-fos was expressed mainly in scattered cells along the luminal surface. Control sections revealed little labeling and confirmed specific staining by the antisense strand, PCNA localization and c-fos expression were similar at days 1, 3, 7 and 28, but at day 14 c-fos was expressed throughout the lesion, with PCNA localized mainly along the luminal edge. The majority of the cells making up the neointima stained rather intensely for alpha-smc actin, identifying them as SMCs. CONCLUSIONS: Results of these experiments indicate that, while c-fos expression correlates with lesion formation, it may be associated with a cellular process distinct from proliferation in this model.

Immunocytochemical localization of androgen receptors in the scalp of the stumptail macaque monkey, a model of androgenetic alopecia.

The purpose of this study was to identify the distribution of androgen receptors in the bald and hairy scalp of adult male and female stumptail macaque monkeys by light microscopic biotin-avidin immunocytochemistry with a highly purified rat monoclonal antibody against the cloned human androgen receptor. Consistent, intense nuclear and minimal cytoplasmic immunostaining was observed in several distinct cell populations of the pilosebaceous unit including the dermal papilla, hair epithelium, outer root sheath, dermal sheath, and sebaceous gland. A similar distribution of androgen receptors was found in miniaturized and terminal anagen and telogen follicles of the bald and hairy scalp, respectively. Binding of androgen receptor antibody was also detected in dermal fibroblasts, basal and intermediate layers of the interfollicular epidermis, and duct and glandular cells of eccrine sweat glands. This investigation demonstrates the presence of androgen receptors in the pilosebaceous unit of the scalp of the stumptail macaque and also shows that their distribution is comparable to that previously reported for humans.

Ultrastructural localization and quantification of extracellular calcium binding sites in mouse vibrissa and human scalp follicles.

The purpose of these experiments was to determine if an extracellular calcium binding site gradient is evident in freshly dissected or cultured mouse vibrissa and human scalp follicles and to measure possible drug effects on this gradient. Mouse vibrissae were cultured with or without either minoxidil or pinacidil, and human scalp follicles were cultured with or without epidermal growth factor. Anagen vibrissa and scalp follicles were dissected and placed in culture for 4 h to 4 days, then fixed in a solution containing lanthanum chloride and prepared for either quantitative energy-dispersive X-ray microanalysis (X-ray) or qualitative transmission electron microscopy (TEM). Since lanthanum has a high charge density it displaces Ca2+ ions from anionic binding sites. TEM analysis revealed extensive accumulation of electron-dense lanthanum deposits in the intercellular compartment of differentiating cells in the hair shaft and inner root sheath in the apex of the follicular bulb. Sparse lanthanum precipitate was observed in the intercellular space of the proliferative cells at the base of the bulb. This gradient of lanthanum precipitate was evident in both freshly dissected and cultured vibrissa and scalp hair follicles, irrespective of treatment with drugs that grow hair or epidermal growth factor. X-ray microanalysis indicated that percent by weight of lanthanum was markedly higher in the apex compared to the base of the follicular bulb in vibrissa and scalp follicles. These qualitative and quantitative data demonstrate that an extracellular calcium binding site gradient exists in cultured vibrissa and scalp hair follicles, and that this gradient is not significantly affected by hair growth altering drugs including minoxidil or pinacidil, and epidermal growth factor.

Measurement of alveolar gas mixing in mechanically ventilated patients.

OBJECTIVE: To evaluate a computer-based, real-time, multibreath nitrogen washout technique in mechanically ventilated patients, incorporating an in-line flow measurement device to measure functional residual capacity and two indices of gas mixing, ventilatory efficiency, and alveolar mixing efficiency. SETTING: ICU, Charing Cross Hospital, London. DESIGN: Within-patient reproducibility of a multibreath nitrogen washout technique. PATIENTS: Seven intubated patients requiring mechanical ventilation. One patient completed two sets of readings. INTERVENTIONS: Patients were connected to a pneumatically driven ventilator fitted with a switching device to be operated either by an appropriate oxygen-nitrogen mixture or equivalently blended oxygen-argon mixture. An inspiratory-expiratory, two-way valve was attached to the delivery port of the ventilator, with a pneumotachograph for flow measurement and a gas sampling probe for gas concentration measurement in line with the patient's endotracheal tube. The analog signals were digitized and handled by a microcomputer. MEASUREMENTS AND MAIN RESULTS: No significant differences were found for any index, with coefficients of variation of 1.5%, 2.9%, and 2.1% for functional residual capacity, ventilatory efficiency, and alveolar mixing efficiency, respectively. CONCLUSIONS: This method gives excellent reproducibility for biological measurements in a clinical setting and shows that these measurements can readily be made on mechanically ventilated patients.

Correction of pneumotachograph signal for changes in viscosity during nitrogen washout.

Changes in gas viscosity during the nitrogen washout test will affect pneumotachograph measurements. A digital correction technique, using estimates of viscosity derived from measurements of gas concentration, has been described and was examined in this study. The pneumotachograph gain varied directly with argon concentration (coefficient of correlation = 0.995, P less than 0.01) indicating that a simple correction was legitimate. This was tested with an in vitro model, giving very consistent estimates of volume (FRC) despite variations in the ventilation pattern, which were slightly underestimated due to incomplete mixing in the system. Alveolar mixing efficiency (AME) was also reproducible but, like studies in man, fell when low tidal volumes were used. In a repeatability study in six volunteers, examined six times on each of two days, FRC and AME were also reproducible (average coefficient of variation within subjects of 4.97% and 4.34% respectively), considerably better than another reported study using conventional flow measurements. This method appears to be a useful addition to existing techniques for studying nitrogen washout.

Responses to changes in filling and contractility of indices of human left ventricular mechanical performance.

1. Beat-by-beat indices of contractility for assessment of inotropic effects in a given subject were studied using pacing with beta-adrenergic blockade, in eight patients undergoing routine left heart catheterization. A catheter-tip manometer was sited in the left ventricle and an electromagnetic velocity transducer was mounted further back on the same catheter so that it was sited in the ascending aorta. 2. The maximum rate of rise of left ventricular pressure (dPLV/dtmax), and of aortic velocity (maximum acceleration, MA) and stroke volume (SV) were all obtained with this catheter. Filling effects were assessed by head-up to head-down tilt, inotropic effects by paced post-extrasystolic potentiation. 3. Tilt produced a mean increase in left ventricular end-diastolic pressure (PLVED) of 8.1 mmHg (P less than 0.05), dPLV/dtmax decreased 4.3% (n.s.), peak velocity (PV) increased 23% (P less than 0.05), MA increased 5.4% (n.s.), and SV increased 17.5% (P less than 0.05). Post-extrasystolic potentiation produced a mean decrease in PLVED of 2.8 mmHg (n.s.), dPLV/dtmax increased 35% (P less than 0.05), PV increased 14% (P less than 0.05), MA increased 55% (P less than 0.05), and SV increased 8.7% (n.s.). 4. There was no difference in response between patients with normal and patients with impaired left ventricular ejection fraction. 5. It is concluded that increased left ventricular filling increases stroke volume greatly (Starling effect) but does not affect dPLV/dtmax, which (together with MA) nevertheless responds markedly to increased contractility. dPLV/dtmax appears to be a volume-insensitive index of contractility in the intact human, whether ejection fraction is normal or impaired.

Validation of beat by beat pulsed Doppler measurements of ascending aortic blood velocity in man.

The volume, velocity, and acceleration of ascending aortic blood were measured in man using a pulsed Doppler ultrasound instrument, with online spectral analysis and offline computer processing of velocity data. This system was firstly validated in a test rig capable of generating pulsatile flow of talc particles in water at physiological velocities and accelerations in a model aorta. Doppler measurements correlated well (r greater than or equal to 0.90) with simultaneous electromagnetic measurements of stroke volume, peak ejection velocity, and maximum acceleration in this rig. In vivo validation was performed firstly by comparing simultaneous Doppler and thermodilution cardiac output (Q) measurements; this yielded the following regression equation: Doppler Q = 0.90 X thermodilution Q + 0.03 litre.min-1, r = 0.92; n = 38. Beat by beat measurements were then validated against simultaneous invasive aortic blood velocity measurements made using a Mills electromagnetic cathetertip probe. When paced single beats of different size were compared within subjects the correlation coefficients between Doppler and electromagnetic measurements averaged 0.89 for stroke volume, 0.91 for peak ejection velocity, and 0.79 for maximum acceleration in five subjects. The absolute values for velocity and acceleration from the Doppler system differed significantly from the absolute values given by the electromagnetic system and this difference was not consistent between subjects. It is concluded that the Doppler system can non-invasively record relative changes in left ventricular ejection in man.

Does beta-blockade directly reduce myocardial oxygen consumption?

This paper describes a method for determining whether beta-blocking agents reduce myocardial oxygen consumption by a direct action on the myocardium in addition to that reduction produced by changes in cardiac mechanical function. Measurements of myocardial oxygen consumption were made in anaesthetized dogs . Changes in heart rate were produced by atropine and by ventricular pacing. Alterations in ventricular loading were achieved by balloon inflations in the descending aorta and by infusions of nitroprusside and dextran. Measurements under these conditions were repeated after beta-blockade. Analysis required the separation of the part of reduced myocardial oxygen consumption resulting from the mechanical effects of beta-blockade from any possible additional direct effect on the myocardium. There was no evidence for a significant direct effect. The average overall reduction in myocardial oxygen consumption after beta-blockade was 18% but the estimated reduction not accountable to mechanical effects was only 2% (range, 95% probability, -7% to 3%).

Sex roles, personality, and intellectual abilities in adolescents.

The relationship between personality variables associated with sex roles and the cognitive variables of math and verbal ability was examined in three groups of adolescents. Masculinity and femininity of interests, behavioral traits, and values were examined using three inventories: the Femininity Scale from the California Psychological Inventory, the Bem Sex Role Inventory, and the Study of Values. Results indicate that there is some evidence for a positive relationship between masculine traits and values and math ability, and feminine traits and values and verbal skills (for both sexes). Certain traits indicative of maturity were found to be positively related to both high math and high verbal scores, while certain highly sex-typed traits and interests were found to be negatively related to both cognitive variables. A different relationship for males and females was found between high intellectual scores and indicators of self-concept and emotional well-being. The differing relationship between each of the three personality variables indicative of sex roles (e.g., interests, values, traits) and cognitive variables emphasizes the need to view masculinity and feminity, as well as "sex-role," as a complex combination of the many different aspects of sex roles as they exist in our society.

Vasodilator effects of sulfinpyrazone in dogs.

The hemodynamic effects of sulfinpyrazone were investigated in 12 anesthetized dogs. Bolus injections into a coronary artery (1--500 mg) and a femoral artery (10--300 mg) and intravenous infusions (10 and 20 mg/min up to 500 mg) were given. After intracoronary injection, coronary dilatation occurred for over 20 min without major changes in cardiac muscle function. Femoral vasodilatation was also induced by local injection. Slow intravenous infusion resulted in inconsistent changes of coronary blood flow. However, in one instance, coronary dilatation was observed at a plasma level of 27.8 microgram/ml, which is comparable with that reached in man after standard oral dosage. Thus, sulfinpyrazone has coronary vasodilator effects which may have relevance to patient therapy.

The absence of protein--sparing effects utilizing crystalline amino acids in stressed patients.

The protein-sparing effects of the peripheral infusion of crystalline amino acids (PAA) was studied metabolically in selected surgical patients subjected to various degrees of stress. Twenty-one patients (sixteen cancer patients receiving chemotherapy and/or radiotherapy, three with major abdominal traumatic injuries and four with paralytic ileus) were infused with 2 1/24 hours of a solution of 4.2% Travasol amino acids with only 5% glucose as a source of nonprotein calories. One-half of the cancer patients were also allowed ad libitum oral intake of a regular hospital diet or Vivonex-HN. The nutritional status was evaluated by measuring changes in body weight, serum albumin levels and nitrogen balance. Body weight decreased in only the trauma patients. When these solutions were the sole source of nutrients all patients were in negative nitrogen balance and had significant decreases in their serum albumin levels. Serum albumin levels were preserved only when extra sources of calories were provided. The infusion of the crystalline amino acids without adequate levels of nonprotein energy did not conserve protein in these stressed patients.

The electromagnetic flowmeter.

The electromagnetic flowmeter, which has developed since its inception into a reliable clinical instrument that has become the standard to which all other flowmeters are compared, is described. Perivascular and intravascular transducers now available, which can easily be used to give reliable, high fidelity recordings of blood flow and velocity, are also discussed.