Evaluating a unique, specialist psychiatric genetic counseling clinic: uptake and impact.

People with psychiatric disorders and their family members have expressed interest in receiving genetic counseling (GC). In February 2012, we opened the first (to our knowledge) specialist psychiatric GC clinic of its kind, for individuals with non-syndromic psychiatric disorders and their families. Prior to GC and at a standard 1-month follow-up session, clinical assessment tools are completed, specifically, the GC outcomes scale (GCOS, which measures empowerment, completed by all clients) and the Illness Management Self Efficacy scale (IMSES, completed by those with mental illness). Consecutive English-speaking clients attending the clinic between 1 February 2012 and 31 January 2013 who were capable of consenting were asked for permission to use their de-identified clinical data for research purposes. Descriptive analyses were conducted to ascertain demographic details of attendees, and paired sample t-tests were conducted to assess changes in GCOS and IMSES scores from pre- to post-GC. Of 143 clients, seven were unable to consent, and 75/136 (55.1%) consented. Most were female (85.3%), self-referred (76%), and had personal experience of mental illness (65.3%). Mean GCOS and IMSES scores increased significantly after GC (p < 0.0001 and p = 0.011, respectively). In a naturalistic setting, GC increases empowerment and self-efficacy in this population.

Parental decisions following prenatal diagnosis of sex chromosome aneuploidy: a trend over time.

Research over the last 20 years has considerably changed the understanding of the natural history and prognosis for individuals with a diagnosis of sex chromosome aneuploidy (SCA). A cross-sectional retrospective analysis of factors influencing parental decisions following a prenatal diagnosis of SCA during the time period of 1971-97 was performed. The records of 169 fetuses with a prenatal karyotype of 45,X, 47,XXX, 47,XXY, and 47,XYY were reviewed. Mosaic karyotypes for SCA were also included. Information reviewed involved: parental decision, the type of SCA, the presence or absence of mosaicism, the presence or absence of a fetal anomaly diagnosed by ultrasound examination, indication for prenatal diagnosis, prenatal procedure performed, parental age, marital status, previous pregnancy history, family history, ethnicity, religion, education, and profession. A significant correlation was found between the decision to continue a pregnancy and the type of SCA and the presence of fetal abnormalities on ultrasound examination. In addition, this study examined differences in parental decisions over time for the years in question. A statistically significant trend was observed with a higher rate of pregnancy continuation in the more recent years.

The importance of congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis.

We describe a family with familial adenomatous polyposis (FAP) and congenital hypertrophy of the retinal pigment epithelium (RPE). Three of five members with FAP showed flat, well-demarcated, round to oval pigmented patches of congenital hypertrophy of the RPE. We stress the importance of congenital hypertrophy of the RPE as a clinical marker in identifying patients with FAP since they are at risk for cancer.

Recurrence risks for near relatives of children with sensori-neural deafness.

In a sample of children with sensori-neural deafness and no evidence of a syndrome, ototoxic exposure, or autosomal dominant or X-linked family history, seen in the Division of Medical Genetics of The Montreal Children's Hospital, the probability of a sibling being similarly affected was about 1 in 6, both in French-Canadian families and the remainder of the sample. The frequency of deafness of early onset was measured in the uncles and aunts of probands, and these figures were used to derive approximate recurrence risks for the offspring of probands (about 1 in 130, ignoring the possibility of autosomal dominant mutation) and for the offspring of the probands' unaffected sibs (about 1 in 250). A rough estimate of the number of autosomal recessive loci contributing to sensori-neural deafness is derived as 13.

The efficacy and safety of dilevalol in patients with chronic stable angina pectoris.

This is the first reported large clinical trial of the antianginal and acute ischemic effectiveness and safety of dilevalol (the R, R-isomer of labetalol) in patients with chronic stable angina pectoris. This was a multicenter double blind fixed-dose parallel group placebo controlled trial. Patients with chronic stable angina and positive and reproducible exercise tests (+/- 20%) were included. If randomized, patients entered one of four fixed dose groups (twice a day placebo, 100 mgm, 200 mgm and 400 mgm bid for 2 weeks). Exercise testing was performed at 2 hours (peak) and 12 hours (trough) postdosing. This was followed by a 2-week once-a-day dosing regimen in which patients received the same total daily dose as the prior 2 weeks, with the full dose in the morning and a matched placebo in the evening. Exercise testing was performed at 2 hours (peak) and 24 hours (trough) postdosing. Anginal frequency and NTG consumption were significantly reduced, and equally so, by qd and bid regimens. The time of exercise to the onset of angina increased and the proportion of patients terminating exercise because of moderate angina decreased in a dose response fashion for both peak and trough tests and for both qd and bid regimens. There was also a dose related decrease in exercise induced ST segment depression and an increase in time to 1 mm ST depression. In 15 patients, 24-hour ambulatory monitoring also revealed a decrease in episodes of silent ischemia. No significant side effects related to the study drug occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Regression of left ventricular hypertrophy in treated hypertensive patients with dilevalol and metoprolol--a double blind randomized study.

This study was designed to evaluate the effects of a new beta-adrenergic blocking agent with beta 2 agonist activity (dilevalol, an R-R' isomer of labetalol) on left ventricular hypertrophy regression as seen by M-mode echocardiography. The study design was a 2:1 double blind randomization of dilevalol versus metoprolol. There was an equal blood pressure reduction in the two groups (supine diastolic blood pressure fell from 101 +/- 4.5 mm Hg to 87 +/- 13.7 mm Hg, P less than .001 in the dilevalol group, and 101 +/- 4.3 mm Hg to 87 +/- 8.6 mm Hg, P less than .01, in the metoprolol group). At the end of 2 months, there was an overall 7.5% decrease in left ventricular mass index in the 16 dilevalol treated patients (this was due to a 4.4% decrease in posterior wall thickness, end diastolic dimension increased by only 1%). Of the seven patients with an increased left ventricular mass index, all demonstrated hypertrophy regression (mean 17.14%). In contrast, no significant change in left ventricular mass was seen in the metoprolol treated group. Echocardiographic left ventricular mass index and electrocardiographic evidence of left ventricular hypertrophy (using the Sokolow-Lyons criteria and Romhilt-Estes point score) had poor correlation (r = .30 and r = .38, respectively). Resting ejection fraction increased by 5% and velocity of circumferential fiber shortening by 14% in the dilevalol treatment group (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

The impact of antianginal drug therapy on asymptomatic myocardial ischemia.

This study addresses the effect of the three major classes of antianginal agents on asymptomatic myocardial ischemia in patients with chronic stable angina pectoris. The authors found that each class (given as monotherapy) resulted in a 50% reduction in asymptomatic ischemia (both in the number of episodes and the ST product). Dual therapy resulted in an overall four fold reduction compared to placebo. Therapy also resulted in a beneficial alteration in the frequency distribution of asymptomatic ischemia. Stratification into three age groups demonstrated an equal prevalence of asymptomatic ischemia in each. All ages had nearly equivalent reductions in asymptomatic ischemia by monotherapy and dual therapy, but the youngest age group seemingly responded better to monotherapy than did the oldest age group.

Safety and efficacy of amlodipine added to hydrochlorothiazide therapy in essential hypertension.

We compared amlodipine, a dihydropyridine calcium antagonist, to placebo as add-on therapy to hydrochlorothiazide in 91 hypertensive patients inadequately controlled on hydrochlorothiazide (50 mg/d for four weeks). This was a double-blind, randomized, multicenter, parallel group-trial; 45 patients received placebo and 46 received amlodipine in doses of 2.5 to 10 mg qd (mean 9 mg/d). Supine blood pressure systolic/diastolic, mean +/- SE mm Hg) 24-hour postdose was significantly reduced by 14.2 +/- 2.3/11.7 +/- 1, compared to placebo, 4.5 +/- 2.7/5 +/- 1.2. Standing blood pressure was similarly reduced: amlodipine by 14 +/- 2.7/12.5 +/- 1.2; placebo by 3 +/- 2.1/5.8 +/- 1.2. This reduction in blood pressure was attained without any significant changes in pulse rate, EKG, and serum lipids (triglycerides were reduced in the amlodipine group by 42.9 mg/dL, P = .023). Only two patients had side effects requiring discontinuation from the study (both in the amlodipine group). Side effects occurred in 27 amlodipine-treated patients (11 with peripheral edema) and 18 patients in the placebo (three with peripheral edema) group. Investigator's assessment of therapeutic effect and tolerability, and the percent of responders v nonresponders was also in favor of amlodipine. Thus amlodipine administered once daily is an effective and safe agent for second-step therapy in mild to moderate essential hypertension.

Predictors of left ventricular hypertrophy in patients with essential hypertension.

The purpose of this study was to assess clinical variables which might be predictive of echocardiographic left ventricular hypertrophy in mildly hypertensive patients. Eighteen patients (mean age 51) were studied following four weeks of hydrochlorothiazide monotherapy. Variables assessed included age, duration of hypertension, body surface area, serum cholesterol, alcohol consumption, smoking, maximum systolic and mean blood pressures, and variability of blood pressure determined from hourly measurements taken 12 hours after hydrochlorothiazide dosing. Using stepwise multiple linear regression (with left ventricular mass index analyzed as a continuous variable), the variability of blood pressure was predictive of an elevated left ventricular mass index (p less than 0.0003, r2 = 0.61). The duration of hypertension added significantly to the variability in predicting an elevated left ventricular mass index (p less than 0.004, multiple r = 0.74). In conclusion, echocardiographic left ventricular hypertrophy was significantly related to the variability of blood pressure recorded hourly for 12 h after subjects received 50 mg of hydrochlorothiazide.

Effects of purine amino groups on the development of Drosophila.

The effect of a variety of 6-substituted purines on development of Drosophila melanogaster, eggs and larva, were studied. Purine and 2,6-diaminopurine both were very toxic to egg development. Adenine and 2,6-diaminopurine were moderately and equally toxic to larva development. Substitution on the 6-position of the purine ring was very effective in regulating metamorphosis of Drosophila.