The amyloid proteins isolated from neuritic plaques and the cerebrovasculature of Alzheimer's disease are self-aggregating moieties termed A4 protein and beta-protein, respectively. A putative A4 amyloid precursor (herein termed A4(695] has been characterized by analysis of a human brain complementary DNA. We report here the sequence of a closely related amyloid cDNA, A4(751), distinguished from A4(695) by the presence of a 168 base-pair (bp) sequence which adds 57 amino acids to, and removes one residue from, the predicted A4(695) protein. The peptide predicted from this insert is very similar to the Kunitz family of serine proteinase inhibitors. The two A4-specific messenger RNAs are differentially expressed: in a limited survey, A4(751) mRNA appears to be ubiquitous, whereas A4(695) mRNA has a restricted pattern of expression which includes cells from neuronal tissue. These data may have significant implications for understanding amyloid deposition in Alzheimer's disease.

Alzheimer Disease↗

PubMed1988

Combining randomized and nonrandomized patients in the statistical analysis of clinical trials.

Explore the source record for details and available documents.

Clinical Trials as Topic↗

PubMed1988

The comprehensive cohort study: the use of registry data to confirm and extend a randomized trial.

There are distinct advantages to the comprehensive cohort design for randomized clinical trials. The design allows the researcher to systematically compare the trial participants and the trial results with the characteristics and results in the population of eligible patients who were not randomly assigned to treatment. There are some problems with this design. The added costs of enrollment and follow-up for the nonrandomized cohort can add substantially to the cost of a trial. As the CASS example illustrates, careful attention must be given to definition of the treatment groups in the nonrandomized cohort. For the randomized patients, group assignment by "intention to treat" is preferred in most cases. The definition of "intention to treat" in the nonrandomized cohort may be difficult, since the patient may receive recommendations from several sources and, in the case of chronic disease, the decision may be postponed for a long period. This problem is not specific to the comprehensive cohort design, however, and a comparison group of concurrently enrolled and followed patients is almost always preferred over a comparison group found elsewhere.

Clinical Trials as Topic↗

PubMed1988

Source origin of a 50-msec latency auditory evoked field component in young schizophrenic men.

We recorded auditory evoked magnetic fields in response to 128 15-msec duration 1-KHz tone pips from both hemispheres of 6 young schizophrenic men. Auditory evoked potentials were recorded conventionally from a vertex lead. The approximately 50-msec latency component was identified in both the magnetic (M50) and electroencephalographic (EEG) (P50) recordings. Isofield topographical contour maps were used to estimate M50 source location and depth. Magnetic resonance imaging was used to identify the neuroanatomical structure(s) present at the estimated source location. M50 sources appeared to reside in the planum temporale in both left and right hemispheres in all subjects. Normal inter-hemispheric asymmetry (with respect to external bony landmarks) of the M50 source was not found in this patient group. Additionally, left (but not right) hemisphere source anatomy differed in several respects from data previously reported in normals.

Adult↗

PubMed1988

Source location of a 50 msec latency auditory evoked field component.

We recorded auditory evoked magnetic fields in response to 128 15 msec duration 1 kHz tone pips from both hemispheres of 6 normal adult males. Auditory evoked potentials were recorded conventionally from a vertex lead. An approximately 50 msec latency component was identified in both the magnetic (called the M50) and EEG (called the P50) recordings. Isofield topographical contour maps were used to estimate M50 source location and depth. With respect to extracranial bony landmarks, M50 source locations were significantly higher and tended to be more posterior, over the left hemisphere. M50 and P50 latencies were not significantly different in 5 of 6 subjects; in one, M50 latencies were significantly longer than P50 latencies over the left hemisphere. Magnetic resonance images in 5 subjects were used to identify the neuroanatomical structure(s) present at the estimated source location. M50 sources appeared to reside in the cortex of the planum temporale in both left and right hemispheres in all 5 subjects.

Adult↗

PubMed1988

Imbalance in treatment assignments in stratified blocked randomization.

Blocking and stratification are used in preparing randomization assignments to ensure that there will be nearly equal numbers of patients in each treatment group and that the groups will be similar with respect to important covariates. Stratified blocked randomization will create near balance within strata, but imbalance for the total trial may still occur. The variance for the total trial imbalance D is derived and examples from clinical trials are given. Under reasonable assumptions, if the blocking factor is size B in each of K strata, then max D = KB/2 and var D = K(B + 1)/6. These results may be used in planning a trial to estimate the overall imbalance expected for various choices of B and K. A conditional variance is given that allows the probability of an observed imbalance at the completion of a trial to be evaluated. Overall imbalance is about as likely with stratified blocked randomization as with simple randomization unless the total sample size N is appreciably larger than K X B. So long as the blinding is maintained, the block sizes should be chosen to be as small as possible.

Analysis of Variance↗

PubMed1988

Ventricular function and infarct size: the Western Washington Intravenous Streptokinase in Myocardial Infarction Trial.

The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Trial randomized 368 patients with symptoms and signs of acute myocardial infarction of less than 6 h duration to either conventional care or 1.5 million units of intravenous streptokinase. The mean time to randomization was 209 min and 52% of patients were randomized within 3 h of symptom onset. Quantitative, tomographic thallium-201 infarct size and radionuclide ejection fraction were measured at 8.2 +/- 7.5 weeks in 207 survivors who lived within a 100 mile radius of a centralized laboratory. Overall, infarct size as a percent of the left ventricle was 19 +/- 13% for control subjects and 15 +/- 13% for treatment patients (p = 0.03). For anterior infarction in patients entered within 3 h of symptom onset, infarct size was 28 +/- 13% in the control group versus 19 +/- 15% for the treatment group (p = 0.09). Left ventricular ejection fraction was 47 +/- 15% in the control versus 51 +/- 15% in the treatment group (p = 0.08). For anterior infarction of less than 3 h duration, the ejection fraction was 38 +/- 16% in the control versus 48 +/- 20% in the treatment group (p = 0.13). By statistical analysis incorporating the nonsurvivors, p values for all of these variables were less than or equal to 0.08. There was no benefit for patients with inferior infarction or for anterior infarction of greater than 3 h duration. It is concluded that intravenous streptokinase, when given within 3 h of symptom onset to patients with anterior infarction, reduces infarct size and improves ventricular function.

Clinical Trials as Topic↗

PubMed1988

Nuclear magnetic resonance imaging: its diagnostic value in patients with congenital vascular malformations of the limbs.

Congenital vascular malformations (CVMs) of the limb include simple and cavernous hemangiomas, microarteriovenous and macroarteriovenous fistulas, venous angiomas, and mixed CVMs. In differentiating these lesions, Doppler waveform analysis, labeled microsphere studies, arteriography, closed-space phlebography, and contrast-enhanced CT scans have all been advocated, but each has significant limitations. This article evaluates the ability of magnetic resonance imaging (MRI) in characterizing CVMs. Limb CVMs were evaluated by MRI in eight patients: four in the upper and four in the lower extremity. Before MRI, seven of the patients had arteriography, five had phlebography, and five had Doppler waveform analysis. MRI showed a highly cellular network with little arteriovenous flow in five patients. In four of these, arteriography and phlebography confirmed the presence of a predominantly venous or microfistulous anomaly. In the other three patients, MRI demonstrated high-flow arterial and venous channels and were confirmed by arteriography to have macrofistulous arteriovenous malformations. In all eight patients, MRI revealed the anatomic location and the longitudinal and transverse extent of the vascular malformation as well as their relationships with contiguous muscle groups, bones, and vessels. We conclude that CVMs of the limbs can be characterized accurately with MRI, with the anatomic extent, degree of cellularity, and flow characteristics readily gauged. Because MRI provides the same basic information supplied by angiography and the noninvasive laboratory and assesses anatomic extent and cellularity, it serves well as the primary diagnostic test for suspected CVMs, particularly in infants and children in whom competitive tests pose additional limitations.

Adolescent↗

PubMed1988

High-frequency percussive ventilation in the management of elevated intracranial pressure.

We evaluated 38 patients with combined head injury and respiratory failure requiring manipulation of mean airway pressure in order to achieve satisfactory oxygenation. All patients were initially maintained on conventional ventilatory support. When entry criteria were met, patients were transitioned to high-frequency percussive ventilation (HFPV) and cardiorespiratory variables were measured. HFPV resulted in a statistically significant decrease in intracranial pressures in patients when ICP remained greater than 15 mm Hg in spite of optimum medical management. Satisfactory oxygenation was obtained at approximately half the level of CPAP and peak inspiratory pressure as that on conventional ventilation. Thus HFPV provides an acceptable alternative method of ventilatory support in patients with combined head injury and respiratory failure.

Adult↗

PubMed1988

Effects of photosensitizer (hematoporphyrin derivative-HPD) and light dose on vascular targets in the albino mouse ear.

Photodynamic damage to normal tissues, including skin, appears to occur by photooxidative damage to the normal microvasculature as the primary target sensitized by HPD bound to the vascular wall or endothelial cell. Initial damage to the microvasculature was measured by the increase in vascular permeability (VP) as measured by Evans Blue dye (EB) extravasation as a function of HPD and laser light (632 nm) dose. Albino, Swiss-Webster mice (female 122-25 g, 5 mice per group) were injected intraperitoneally (IP) with incremental doses of HPD (Photofrin II, Photofrin Medical, Inc.) (1, 10, 20, 30, 40 and 50 mg/kg). After 48 hours the left ear of each mouse was masked as a control and the right ear was irradiated at 632 nm using the Aurora-Lexel Argon-dye laser (Cooper Laser Sonics, Inc.) with an intensity of 50 mW/cm2 and light doses of 0, 25, 50, 75, and 100 J/cm2 directed to a 3-mm spot on the mouse ear. No EB leakage occurred in the absence of HPD at any light dose or in the absence of light at any HPC dose. Vascular permeability increased as a function of HPD dose up to 30 mg/kg. AT 50 mg/kg HPD, there was a decrease in VP. At each HPD dose above 10 mg/kg, the VP increased as a function of light dose up to 75 J/cm2. Further increase in light dose was without effect. The amount of HPD porphyrin recovered from irradiated ears decreased as a function of light dose. There appeared to be an irreversible photo destruction of the porphyrin exposed to light.

Capillary Permeability↗

PubMed1988