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Biomedical subjects

D L Holmes

Publications and source records attributed to D L Holmes.

9 recordsLinked to original sources

Expression of growth factor mRNA in rabbit PVR model systems.

Proliferative vitreoretinopathy (PVR) involves the formation of intravitreal fibrocellular membranes which may lead to traction retinal detachment and blindness. The cellular component of epiretinal membranes originates from the proliferation and migration of cells within the eye. Several growth factors and other cytokines are plausible candidates for directing the processes leading to membrane formation. A reproducible animal model is needed for experimental studies of cytokine expression during PVR induction or treatment. We found that intravitreal injection of > 10(6) mixed mononuclear leukocytes or adherent monocytes along with a trans-scleral incision through the pars plana leads to the development of PVR-like disease in rabbit eyes. The severity of the disease was related to the number of monocytes injected. Typically, organized membranes extending from the incision toward the optic nerve formed within one week. Progression to extensive traction retinal detachment required 1 to 4 weeks. Injection of up to 5 x 10(6) lymphocytes or freeze-thaw killed monocytes was ineffective, and coinjecting 100 micrograms endotoxin with the monocytes did not result in enhanced disease. The histological appearance of the epiretinal membranes was similar to human PVR membranes. Macrophage, cytokeratin-positive (epithelial), and fibroblast-like cells were present. Northern blot analysis of RNA extracted from the rabbit membranes revealed the presence of mRNA for acidic fibroblast growth factor (aFGF). Acidic FGF mRNA was not expressed by the injected monocytes. A comparable level of aFGF mRNA and also mRNAs for basic FGF, platelet-derived growth factor-B, and transforming growth factor beta were found in epiretinal membranes induced by a scleral incision in association with cryopexy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Angiotensin-converting enzyme inhibitor therapy and diabetic retinopathy.

This pilot project suggested that angiotensin-converting enzyme (ACE) inhibitors may have an effect on delaying or reversing diabetic retinopathy. One patient who had Grade 5 (preproliferative) retinopathy improved to Grade 2 (microaneurysms only) after two years of treatment. Of the 450 patients followed in our eye and kidney clinic, no other patient showed a similar reversal from Grade 5 retinopathy without treatment. Improvement by one or more grades was seen in three other patients with variable grades of retinopathy after a mean of 3.3 years of treatment. Improvement was not related consistently to a decrease in blood pressure (0 of 4), better glycemic control (2 of 4), or reduction in albumin excretion rate (0 of 4). Proper double-blind controlled studies are needed to prove the effect of ACE inhibitors on diabetic microangiopathy of the eye.

Adolescent

Estimation of polyacrylamide gel pore size from Ferguson plots of normal and anomalously migrating DNA fragments. I. Gels containing 3% N,N'-methylenebisacrylamide.

The mobilities of normal and anomalously migrating DNA fragments were determined in polyacrylamide gels of different acrylamide concentrations, polymerized with 3% N,N'-methylenebisacrylamide as the crosslinker. The DNA samples were a commercially available 123-bp ladder and two molecular weight ladders containing multiple copies of two 147-base pair (bp) restriction fragments, obtained from the MspI digestion of plasmid pBR322. One of the 147 bp fragments is known to migrate anomalously slowly in polyacrylamide gels. Ferguson plots were constructed for all multimer ladders, using both absolute mobilities and relative mobilities with respect to the smallest DNA molecule in each data set. If the retardation coefficients were calculated from the relative mobilities, and the rms radius of gyration was used as the measure of DNA size, the Ogston equations were obeyed and the gel fiber parameters could be calculated. The effective pore sizes of the gels were estimated from the gel concentration at which the mobility of a given DNA molecule was reduced to one-half its mobility at zero gel concentration. The estimated pore radii ranged from approximately 130 nm for 3.5% gels to approximately 70 nm for 10.5% gels. These values are much larger than the pore sizes previously determined for the polyacrylamide matrix.

Acrylamides

Estimation of polyacrylamide gel pore size from Ferguson plots of linear DNA fragments. II. Comparison of gels with different crosslinker concentrations, added agarose and added linear polyacrylamide.

The mobilities of various DNA fragments in two normally migrating molecular weight ladders were studied in polyacrylamide gels containing different concentrations of the crosslinker N,N'-methylenebisacrylamide (Bis). The acrylamide concentration ranged from 2.5-10.5%T (w/v); the Bis concentration ranged from 0.5-10%C (w/w), with respect to total acrylamide. Ferguson plots were constructed for each of the DNA fragments in gels of each composition. The Ferguson plots of the different multimers in each molecular weight ladder were nearly parallel in gels containing 0.5-3%C, converged close to a common intercept at zero gel concentration in gels containing 4%C, and crossed at approximately 1.5%T in gels containing 5 and 10%C. If the mobilities observed for the different DNA fragments at zero gel concentration were also extrapolated to zero DNA molecular weight, a common limiting mobility was observed in gels of all crosslinker concentrations. This limiting mobility was approximately equal to the free solution mobility of DNA. The effective pore radius of each gel was estimated from Ferguson plots based on relative mobilities, using the mobility of the smallest DNA fragment in each molecular weight ladder as the reference mobility. The calculated gel pore radii ranged from 142 nm to 19 nm, respectively, for gels containing 4.6%T, 1.5%C, and 10.5%T, 5 or 10%C. These pore radii are an order of magnitude larger than previously accepted values, but are consistent with scanning electron microscope measurements (Rüchel, R., et al., J. Chromatogr. 1978, 42, 77-90).(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylamides

Social policy on the use of aversive interventions: empirical, ethical, and legal considerations.

In an effort to address the controversy regarding the use of aversive interventions in the treatment of individuals with developmental disabilities, this paper presents a review of the literature on the efficacy of such interventions, along with brief reviews of the ethical and legal issues involved. In general, there appears to be empirical, ethical, and legal support for the continued availability of aversive interventions as treatment options, but only if sufficient safeguards are in place.

Autistic Disorder

Pre-spiking dialysate bags: improved peritonitis prevention in patients on CAPD.

We review experience with 238 patients over 5.5 years to determine the impact of techniques of spiking dialysis bags in advance of their use (pre-spiking) on peritonitis incidence. Our two units provide peritoneal dialysis therapies only with liberal patient acceptance policies. The Y-set was used almost exclusively over the last 4 years (192/238 patients), peritonitis rate 1:31.5 patient-months (99 episodes/3,122 months). Nineteen patients spiked each exchange, 23 episodes/282 months, 1:12.3; 173 pre-spiked 1-14 days in advance using Y-set and compact exchange device (CXD), 76 episodes/2,840 months, 1:37.4. Peritonitis rates did not worsen with increased pre-spiking intervals: 1 day, 1:16.2; 2-6 days, 1:47.9; 7 days, 1:62.2; 8-14 days, 1:34.3. Similarly, pre-spiking in CCPD patients at 10 day intervals (4 patients) yielded a peritonitis rate of 1:19. We conclude that pre-spiking dialysis bags using the Y-set and CXD promotes significant peritonitis prevention. By spiking at less frequent intervals, technical performance improves, exchanges are simplified and done under more flexible circumstances. Participation by patient-assistants is facilitated. Transfer from CAPD to CCPD is decreased. Low peritonitis rates contribute to excellent patient acceptance and retention. The potential CAPD-eligible population is broadened.

Adolescent

Searching for multiple targets simultaneously: is it really possible?

In an attempt to clarify the findings of Neisser and his associates with respect to parallel processing of multiple target items in a visual search task, subjects were tested in a multiple-target search situation in which the various target sets were not nested. 20 sessions were run for each subject with 12 trials per day. The targets used were geometric forms, allowing for manipulation of the number of features in each form. The results do not confirm those of Neisser, in fact, the interaction of session x target-set size was in a direction opposite to that predicted by a parallel preattentive processing may in fact have reflected a tendency for subjects to scan for a master set of targets, regardless of which subset of that set was actually present on a given set.

Adult

Use of constant target sets in visual search tasks.

54 subjects participated in a visual scanning study in which each subject was provided with only a single target set (of 1, 2, 4, 6, 8, or 10 letters in length). Eight sessions of 30 trials each were completed for each subject. Although there were slight differences in the rate at which performance improved over trials, this was not systematically related to size of target set. Moreover, even in the last session, there were large differences in performance in the different target sets. These findings suggest that Neisser's evidence for parallel preattentive processing in such tasks may have been confounded by his use of nested target sets and a within-subject design.

Adult

An evaluation of the use of spelling error analysis in the diagnosis of reading disabilities.

This study examined whether significant differences could be observed in types of errors made by normal versus retarded readers (fifth graders) on the WRAT spelling test. Although researchers have reported high numbers of certain types of errors, such as reversals, this study revealed that the proportion of errors attributed to any particular error type is virtually identical for both normal and retarded readers. Retarded readers were thus shown to be unlike normal readers in the number of errors committed but like normal readers in the types of errors committed.

Child