The readability of informed consent forms for research studies conducted in South Africa.

BACKGROUND: Informed consent forms (ICFs) are used to obtain consent from participants. However the complexity and comprehensiveness of these forms may not be appropriate. Readability can be quantified by formulas in Microsoft (MS) Word, such as the Flesch Reading Ease test. The South African (SA) ethics guidelines suggest that the MS Word Flesch-Kincaid Reading Grade score should be used to assess the complexity of ICFs and should be the equivalent of grade 8 level, or lower. OBJECTIVES: To use readability formulas to determine whether current SA ICFs are appropriate for the general population. METHODS: This was a descriptive study of a sample of English ICFs (solicited from our studies, as well as from local researchers) which received approval from local ethical review boards during the past 5 years, for prospective (≥6 months) drug studies that explored treatment and prevention of HIV, tuberculosis, diabetes or cardiovascular disease. ICFs were evaluated in MS Word for Flesch Reading Ease and Flesch-Kincaid Reading Grade, with the Simple Measure of Gobbledygook (SMOG) index calculated using www.readabilityformulas.com. Recommended targets for easy readability are above 60 for the Flesch Reading Ease score, and less than or equal to a grade 8 reading level for the Flesch-Kincaid Reading Grade and SMOG. RESULTS:   A total of 75 consent forms from 35 individual research studies conducted in SA over the last 5 years were included. The consent forms had been approved by six ethics committees across seven of the SA provinces. The median (interquartile range (IQR)) Flesch Reading Ease score was 55.8 (48.7 - 59.7) and 18 (25.0%) of the ICFs had easy or standard readability, while the median (IQR) Flesch-Kincaid Grade was 10.2 (8.8 - 11.4), with 23 (30.6%) at least a grade 8 level or lower. The median (IQR) SMOG index was 9.8 (9.0 - 11.1) and 4 (5.3%) scored below grade 8 level. CONCLUSIONS: Two-thirds of the ICFs from this study fail to meet the SA readability standard, a result matched by using alternative readability formulas. Readability can be improved with simple techniques and by actively monitoring readability metrics.

Safety and effectiveness of a single and repeat intramuscular injection of a GnRH vaccine (GonaCon™) in adult female domestic cats.

Sterilization is a key strategy to reduce the number of domestic cats entering and killed in shelters each year. However, surgical sterilization is expensive and labour-intensive and cannot fully address the 70 million free-roaming cats estimated to exist in the United States. GonaCon™ is a gonadotropin-releasing hormone vaccine originally developed for use as a wildlife immunocontraceptive. An earlier formulation was tested in domestic cats and found to be safe and effective for long-term contraception. However, the current Environmental Protection Agency (EPA)-registered formulation consists of a different antigen-carrier protein and increased antigen concentration and has never been tested in cats. A pilot study was undertaken to evaluate the short-term safety of a single GonaCon immunization, assess the consequences of vaccinated cats receiving an accidental second GonaCon injection and determine the humoral immune response to immunization. During Phase 1, cats in Group A (n = 3) received a single intramuscular injection of GonaCon and Group B (n = 3) received a single intramuscular injection of saline. During Phase 2, Group A received a second GonaCon injection and Group B received their initial GonaCon injection. All cats developed GnRH antibodies within 30 days of vaccine administration. The endpoint titre (1:1,024,000) was similar among all cats, and levels remained high throughout the duration of the study. Four cats developed a sterile, painless, self-limiting mass at the site of injection. The mean number of days to mass development was 110.3 (range, 18-249 days). In conclusion, this preliminary study suggests that the EPA-registered GonaCon formulation is safe for continued testing in domestic cats, an accidental revaccination should not increase the risk of a vaccine reaction and the EPA-registered formulation effectively elicits a strong humoral immune response.

Estimates of heterosis for in vitro embryo production using reciprocal crosses in cattle.

In vitro embryo production and exploitation of heterosis are two methods of increasing productivity and accelerating genetic progress in many cattle production systems. However, it is not known if heterosis exists in bovine embryos produced in vitro. Tests for heterosis in in vitro embryo production were conducted in two experiments using reciprocal crosses. In the first, gametes from Bos taurus and Bos indicus were used; in the second, gametes from dairy and beef breeds of Bos taurus were used. In each experiment, both parental groups were used as sperm and oocyte donors, producing crossbred and purebred embryos. Oocytes obtained from abattoir-derived ovaries underwent in vitro maturation and in vitro fertilization with frozen semen. Embryos were cultured to blastocyst stage and observed. In the first experiment, higher (P < 0.05) rates of blastocyst formation were found for Bos taurus both as sires and as dams. Approximately 36% of the purebred Bos taurus oocytes and 21% of the purebred Bos indicus oocytes developed to blastocyst. Crosses averaged 16% resulting in a heterosis estimate of 45%. Ovaries from Bos indicus cows had more harvestable oocytes than did those from Bos taurus cows (P < 0.05). No evidence for heterosis was found for crosses within Bos taurus. Oocytes from beef cows had a higher rate of blastocyst formation than did those from dairy cows (30 vs. 24%, P < 0.05). These seemingly disparate results concerning heterosis were discussed in light of the period of genetic isolation of the parental populations in the two experiments.

Identification of discriminator base atomic groups that modulate the alanine aminoacylation reaction.

Specific aminoacylation of tRNAs involves activation of an amino acid with ATP followed by amino acid transfer to the tRNA. Previous work showed that the transfer of alanine from Escherichia coli alanyl-tRNA synthetase to a cognate RNA minihelix involves a transition state sensitive to changes in the tRNA acceptor stem. Specifically, the "discriminator" base at position 73 of minihelix(Ala) is a critical determinant of the transfer step of aminoacylation. This single-stranded nucleotide has previously been shown by solution NMR to be stacked predominantly onto G(1) of the first base pair of the alanine acceptor stem helix. In this work, RNA duplex(Ala) variants were prepared to investigate the role of specific discriminator base atomic groups in aminoacylation catalytic efficiency. Results indicate that the purine structure appears to be important for stabilization of the transition state and that major groove elements are more critical than those located in the minor groove. This result is in accordance with the predicted orientation of a class II synthetase at the end of the acceptor helix. In particular, substitution of the exocyclic amino group of A(73) with a keto-oxygen resulted in negative discrimination at this site. Taken together, these new results are consistent with the involvement of major groove atomic groups of the discriminator base in the formation of the transition state for the amino acid transfer step.

Visualization of the diffusion of metal ions and organic molecules by magnetic resonance imaging of water.

Null point magnetic resonance imaging (MRI) of water has been used to map the location in space and time of small concentrations of paramagnetic metals and nitroxide free radicals. Any paramagnetic species whose effective magnetisation is dependent on the chemical potential of the surrounding medium, can be used either as a "molecular amplifier" or as an "MRI-active indicator"-This approach has been used to study the diffusion of acid (via (Cu EDTA)), and of oxidising and reducing agents (via Fe(II), Fe(III), ions) in a range of hydrogels and in hen-knee cartilage.

Visualisation of mass transport of small organic molecules and metal ions through articular cartilage by magnetic resonance imaging.

Magnetic resonance imaging of water has been used to visualise the migration of three paramagnetic species, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (4-hydroxy-TEMPO, 1), Cu2+ ions, and copper ethylenediamine-tetraacetate (CuEDTA, 2) through cartilage on the femoral condyle of the chicken knee. The migration of copper ions is dominated by strong binding with the cartilage. In contrast, both 1 and 2 bind weakly, and their diffusion can be followed as a progressive wave through the cartilage and subsequently into the trabecular bone structure.

Quantification of differences in frequency content of signal-averaged electrocardiograms in patients with compared to those without sustained ventricular tachycardia.

To quantify differences in the frequency content of signal-averaged electrocardiograms between patients with and without sustained ventricular tachycardia (VT), the energy spectra of the terminal QRS and ST segments of signal-averaged orthogonal ECGs were computed in 3 groups of patients by squaring the magnitude of the fast-Fourier transformed data. The terminal 40 ms of the QRS complex and ST segment were analyzed as a single unit to enhance frequency resolution. Group I comprised 23 patients with documented, remote myocardial infarction who had manifested subsequent episodes of sustained VT; group II comprised 53 patients with previous, remote infarction without subsequent sustained VT; and group III comprised 11 normal subjects. The terminal QRS and ST segments from patients with sustained VT contained a 10- to 100-fold greater proportion of components in the 20- to 50-Hz range compared with corresponding electrocardiographic segments in patients without VT. There were no significant differences in the peak frequencies among patient groups. However, the relative contribution of the magnitudes of these peak frequencies to the overall maximum magnitude of the spectral plot differed significantly (p less than 0.0001). No frequencies above 50 Hz contributed substantially to the energy spectra of the terminal QRS and ST segments in any group. Thus, differences in the energy spectra do not result from differences in the frequencies of components, but are attributable instead to differences in the amplitudes of components within a relatively narrow range of frequencies. The quantitative approach developed should provide objective indexes for assessing effects of antiarrhythmic interventions on abnormalities recognizable by frequency-domain analysis and improve noninvasive definition of risk for development of sustained VT.

Myocardial preservation with nifedipine: a comparative study at normothermia.

Sixty-four dogs were placed on normothermic total cardiopulmonary bypass, and global ischemia was induced for 1 hour during which continuous infusions (240 ml per hour) (N = 39) or bolus injections (150 to 200 ml every 30 minutes) (N = 23) into the proximal aortic root were performed. The control groups (N = 26) had infusion or injection of normal saline solution, normal saline solution + 25 mEq/L of potassium chloride, or Normosol-R pH 7.4. The cardioplegic solution (N = 15) contained 25 mEq/L of potassium chloride in Normosol-R pH 7.4, 0.25 mg/ml of lidocaine, 500 mg/dl of glucose, and 1.8 microU/ml of insulin. The nifedipine group (N = 23) had infusion or injection of 0.167 to 0.2 microgram/ml of nifedipine in saline solution, Normosol-R pH 7.4, or the cardioplegic solution. Left ventricular performance was assessed by phasic and mean measurements of left ventricular peak and end-diastolic pressures and its first derivative, left and right atrial pressures, and ascending aortic blood flow. Calculations of stroke work index and total peripheral resistance were performed. Morphological examinations, and light and electron microscopic examinations of heart slices were done. The results demonstrated a consistent superiority of the nifedipine group in terms of performance after bypass compared with the cardioplegic or control group. Normal preischemic stroke work indices and Sarnoff curves were present 2 hours after bypass for the nifedipine-treated groups. The cardioplegic solution was ineffective when given continuously but gave modest protection when given as a bolus injection. It is concluded that the concept of the efficacy of calcium blockade during ischemia and the initial reperfusion period for enhanced myocardial protection is valid.

Nifedipine: a myocardial protective agent.

The effectiveness of the calcium antagonist nifedipine in preserving postischemic myocardial function and structural integrity was experimentally demonstrated in isolated rabbit hearts, in conscious dogs subjected to myocardial infarction, in open chest anesthetized dogs with normothermic regional ischemia induced for 1 to 2 hours and in dogs undergoing hypothermic global ischemia for 2 hours followed by 2 hours of reperfusion. Nifedipine had a beneficial effect on postischemic myocardial stiffness and mitochondrial calcium accumulation, which were correlated. Administration of nifedipine at the onset of myocardial infarction increased blood flow to ischemic zones of myocardial infarction and resulted in less loss of creatine kinase. It reduced by two- to three-fold the volume of the ischemia-reperfusion injury induced by left anterior descending coronary arterial occlusion and release and preserved indexes of hemodynamic function. Nifedipine was found effective in protecting myocardial performance and structure after 2 hours of global ischemia during hypothermic cardiopulmonary bypass. It is suggested that this agent may be useful as an adjunct to cold cardioplegia in man for enhanced myocardial protection during cardiac surgery.