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Biomedical subjects

C A Johnson

Publications and source records attributed to C A Johnson.

At least 199 records · Page 11Linked to original sources
PubMed1994

Individual differences in risk of child abuse by adolescent mothers: assessment in the perinatal period.

Abuse risk potential and parenting attitudes of 66 adolescent mothers were examined during the perinatal period using self-report instruments. Approximately one-half of the sample was considered to be at significant risk. Specific risk factors included distress, rigidity in parenting attitudes, and inappropriate expectations of children. Younger adolescents were at greater risk of abuse, advocated the use of physical punishment more strongly, and reported greater unhappiness than older adolescents. Teens reporting limited social support were also at greater risk for abuse. Low acceptance of the pregnancy was related to abuse potential for parenting, but not pregnant, adolescents. A history of maltreatment was related to self-reported problems with family members but not to overall risk. Implications for the prevention of abuse among adolescent mothers are discussed.

Adolescent↗
PubMed1994

Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase.

Factors developed during the routine storage of whole blood and packed red blood cells that primed the neutrophil (PMN) reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase significantly by 2 weeks of storage, with maximal priming activity by product outdate (2.5 to 3.7 fold). These agents appeared to be generated by cellular constituents because stored, acellular plasma did not demonstrate PMN priming. The priming activity was soluble in chloroform. Priming of the oxidase by plasma and plasma extracts was inhibited by WEB 2170, a platelet-activating factor (PAF) receptor antagonist. Separation of the chloroform-soluble compounds from plasma by normal phase high-performance liquid chromatography demonstrated two peaks of priming activity at the retention times of neutral lipids and lysophosphatidylcholines (lyso-PCs) for both whole blood and packed red blood cells. Analysis of the latter peak of PMN priming by fast atom bombardment mass spectroscopy identified several specific lyso-PC species including C16 and C18 lyso-PAF. Further evaluation by gas chromatography/mass spectroscopy demonstrated that three of these species increased dramatically over product storage time, while the other two species increased modestly, and paralleled the increase in priming activity. Commercially available, purified mixtures of these lyso-PCs primed the PMN oxidase by twofold. When PMNs were incubated with this mixture of lyso-PCs, acetylated analogs of these compounds rapidly accumulated. Thus lipids, including specific lyso-PC species, develop during routine storage of cellular blood components, prime PMNs, and possibly play a role in the severe complications of transfusion therapy.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1993

Studies on analogues of classical antifolates bearing the naphthoyl group in place of benzoyl in the side chain.

Analogues of classical antifolates with the 4-aminobenzoyl group replaced by 4-amino-1-naphthoyl were synthesized for study after molecular modeling indicated ample spatial accommodation for the naphthalene ring and even larger groups in models based on reported X-ray crystallographic data describing the binding of methotrexate to human dihydrofolate reductase (DHFR). The side-chain precursors, N-(4-amino- and 4-(methylamino)-1-naphthoyl)-L-glutamic acid diethyl esters, were synthesized, and the 2,4-diamino-substituted heterocyclic groups were attached using several methods. Target compounds included naphthoyl analogues of aminopterin (AMT), methotrexate (MTX), 5-deazaAMT, 5-deazaMTX, 5-methyl-5-deazaAMT, 5-methyl-5-deazaMTX, and 5,8-dideazaAMT. A 5,6,7,8-tetrahydronaphthoyl analogue of 5-deazaAMT was also prepared. None of the naphthoyl analogues showed loss in binding to DHFR compared with the corresponding antifolate bearing the benzoyl group, thus confirming the anticipated bulk tolerance. Only the 5,6,7,8-tetrahydronaphthoyl analogue displayed reduced antifolate effects. Substrate activity toward folylpolyglutamate synthetase was, however, severely compromised. The naphthoyl compounds were transported into L1210 cells 3-6 times more readily than MTX, and despite apparently low levels of intracellular polyglutamylation, each compound was found to be significantly more potent than MTX in inhibiting tumor cell growth in vitro in three lines (L1210, HL60, and S180). The MTX, 5-methyl-5-deazaAMT, and 5-methyl-5-deazaMTX analogues were evaluated in vivo alongside MTX against E0771 mammary adenocarcinoma in mice. All three proved more effective than MTX in retarding the tumor growth. The naphthoyl analogue of 5-deazaAMT strongly inhibited DHFR from Pneumocystis carinii, Toxoplasma gondii, and rat liver giving IC50 (pM) values of 0.53, 2.1, and 1.6 respectively, but this compound did not inhibit in vitro growth of T. gondii, thus indicating lack of transport.

Aminopterin↗
PubMed1993

Computerized topographic analysis of the healing graft after penetrating keratoplasty for keratoconus.

After penetrating keratoplasty, visual rehabilitation can be slow and is largely a function of corneal surface configuration. Computerized topographic analysis allows the detailed study of corneal surface factors that determine the optical function of the graft. We performed a prospective, longitudinal study of eight patients with keratoconus by using computerized topographic analysis to determine the rate and pattern of postoperative surface normalization and stabilization. Study data included Snellen visual acuity, contrast sensitivity function, central keratometry, photokeratoscopy, and computerized topographic analysis. Data were collected preoperatively and at one week, one month, two months, three months, and six months postoperatively. Results demonstrate that the greatest configurational changes both topographically and functionally occur in the first month after keratoplasty. The computer-generated surface asymmetry index and the surface regularity index correlated well with improvement in Snellen visual acuity measurements. Contrast sensitivity function was depressed initially but improved to well above preoperative values by one month postoperatively and paralleled the improvement in the surface indices and visual acuity. The axis of astigmatism stabilized by one month postoperatively. Our data indicate that topographic analysis provides a good indication of the rate and course of optical stabilization during the early healing process after keratoplasty and correlates well with visual function in the otherwise normal eye.

Adult↗
PubMed1993

Baseline visual field profile of optic neuritis. The experience of the optic neuritis treatment trial. Optic Neuritis Study Group.

The purpose of the present study was to determine the baseline visual field characteristics in 448 patients with acute optic neuritis who were entered into the Optic Neuritis Treatment Trial. The severity and pattern of visual field loss in both the affected and fellow eyes were classified. For affected eyes, diffuse visual field loss was present in 48.2% of eyes, central or centrocecal scotoma was present in 8.3% of eyes, altitudinal or other nerve-fiber bundle-type defects were present in 20.1% of eyes, and a variety of other defects were present in 23.4% of eyes. Visual field involvement was present in the fellow eye at baseline in 308 (68.8%) of the 448 patients. Evidence of a chiasmal or retrochiasmal visual field defect was present in 2.9% of the patients. Since a wide variety of visual field defects can occur with an acute attack of optic neuritis, the pattern of visual field loss is of limited utility in distinguishing optic neuritis from ischemic optic neuropathy and other optic nerve disorders. Asymptomatic visual field defects in the fellow eye are common.

Acute Disease↗
PubMed1993

Blue-on-yellow perimetry can predict the development of glaucomatous visual field loss.

OBJECTIVE: The purpose of this investigation was to determine whether blue-on-yellow (B/Y) perimetry is capable of predicting the onset and location of impending glaucomatous visual field loss in patients with ocular hypertension. DESIGN: A Humphrey Field Analyzer (Humphrey Instruments, San Leandro, Calif) was modified to perform B/Y perimetry to isolate and measure the sensitivity of short-wavelength-sensitive mechanisms. Participants were tested annually with standard white-on-white (W/W) and B/Y automated perimetry for a period of 5 years. PATIENTS: The study population consisted of 38 patients with ocular hypertension and 62 age-matched normal control subjects. RESULTS: Initially, all 76 ocular hypertensive eyes had normal W/W automated perimetry results, with 67 eyes having normal and nine eyes having abnormal B/Y test results. Five years later, five of the nine ocular hypertensive eyes with initial B/Y abnormal results developed glaucomatous visual field loss measured by standard W/W automated perimetry, while none of the 67 ocular hypertensive eyes with initially normal B/Y results developed abnormal W/W perimetry results. CONCLUSIONS: Blue-on-yellow perimetry deficits are an early indicator of glaucomatous damage and are predictive of impending glaucomatous visual field loss for standard W/W automated perimetry. To our knowledge, this is the first prospective, long-term longitudinal study that demonstrates the ability to predict the onset of glaucomatous visual field loss in patients with ocular hypertension on the basis of psychophysical testing.

Adult↗
PubMed1993

Progression of early glaucomatous visual field loss as detected by blue-on-yellow and standard white-on-white automated perimetry.

OBJECTIVE: To determine whether blue-on-yellow perimetry reveals progression of glaucomatous damage before it is evident with standard white-on-white perimetry. DESIGN: A Humphrey field analyzer (Humphrey Instruments, San Leandro, Calif) was modified to perform blue-on-yellow perimetry to isolate and measure the sensitivity of short wavelength-sensitive mechanisms. Participants were tested annually with standard white-on-white automated perimetry and blue-on-yellow automated perimetry for 5 years. PATIENTS: Sixteen patients with early glaucomatous visual field loss in one or both eyes and 62 age-matched normal control subjects. RESULTS: At baseline, 25 (78.1%) of the 32 eyes exhibited larger deficits with blue-on-yellow perimetry, five (15.6%) had equivalent loss with both tests, and two (6.3%) had larger deficits with standard white-on-white perimetry. Seven (21.9%) of the 32 eyes demonstrated evidence of progressive visual field loss with standard white-on-white perimetry in 5 years, while the other 25 eyes (78.1%) were relatively stable. Deficits with blue-on-yellow perimetry were twice as large as deficits with white-on-white perimetry in the stable group and were three to four times as large in the group with progressive field loss. CONCLUSIONS: Blue-on-yellow perimetry is effective in predicting which patients with early glaucomatous visual field loss are most likely to have progressive loss. The rate of progressive loss is greater with blue-on-yellow perimetry than with standard white-on-white perimetry.

Adult↗
PubMed1993

Neuronal vacuolization and necrosis induced by the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK(+)801 (dizocilpine maleate): a light and electron microscopic evaluation of the rat retrosplenial cortex.

MK(+)801 (dizocilpine maleate) is a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor, the major glutamate receptor at excitatory synapses in the central nervous system. Since NMDA antagonists are neuroprotective, there is interest in their development for treatment of cerebral ischemia. Unfortunately, many of these compounds also induce vacuole formation in neurons of the rat retrosplenial cortex (Olney et al., Science 244: 1360-1362, 1989). Although vacuolization was initially reported to be reversible with MK(+)801, preliminary data later suggested that higher doses might produce neuronal necrosis. To explore this issue, young male Sprague-Dawley rats were given a single subcutaneous dose of vehicle or 1, 5, or 10 mg/kg MK(+)801. At 4 h and 1, 2, 3, 4, 7, and 14 days postdose (DPD), the retrosplenial cortex was examined by light and electron microscopy. At 4 h, vacuoles occurred in neurons of retrosplenial cortical layers 3 and 4 in all rats given MK(+)801. Mitochondria and endoplasmic reticulum contributed to vacuole formation. At 1 DPD, vacuoles or necrotic neurons were rarely observed. At all subsequent time points, necrotic neurons were readily evident in rats given 5 or 10 mg/kg MK(+)801, but only rarely evident in rats given 1 mg/kg. Necrotic neurons were associated with reactive microglial cells that contained electron-dense debris ultrastructurally. If similar dose-dependent neuronal necrosis proves to be a feature of other NMDA antagonists, such effects might raise concerns for the development and use of these compounds in human cerebrovascular diseases.

Animals↗
PubMed1993

Automated perimetry and short wavelength sensitivity in patients with asymmetric intraocular pressures.

Automated visual field testing [white-on-white (W-on-W) perimetry] and perimetry of short wavelength sensitive mechanisms [blue-on-yellow (B-on-Y) perimetry] were conducted in both eyes of patients with large asymmetries in intraocular pressure (IOP) between eyes (average difference = 19.9 mm Hg). Overall visual field sensitivity was significantly (P < 0.05) depressed in the eyes with higher IOP by an average of 2.33 dB, in spite of the fact that all but two of the eyes with higher IOP demonstrated visual field sensitivities that were within normal limits. None of the eyes with lower IOP were outside of normal sensitivity limits. B-on-Y perimetry revealed similar findings, except that three of the fellow eyes with relatively lower IOP also demonstrated abnormalities. Our results are consistent with the hypothesis that the diffuse loss in visual field sensitivity in glaucoma is related to IOP. In addition, it appears that short wavelength sensitive mechanism may reveal early glaucomatous losses in patients with elevated IOP.

Adult↗
PubMed1993

Medicine on British television: a content analysis.

Fifty-four British television programs on medical topics were viewed and analyzed during a four-month period in the winter of 1988-89. Medical programs of a nonfictional, nondramatic variety were represented on all four channels of British television with 75% appearing on the BBC. The primary format was that of a documentary; most offerings were during peak television viewing hours and were 30-50 minutes in length. Principal settings were within the realm of clinical medicine or health care delivery. The location of filming was in hospitals rather than outpatient areas. Doctors were presented as experts, but general practitioners were infrequently represented. The health care team was generally treated in a sympathetic manner. Psychiatric/behavioral and neurologic topics appeared frequently, with common medical problems and preventive medicine rarely emphasized.

Attitude to Health↗
PubMed1993

Compounds biologically similar to platelet activating factor are present in stored blood components.

Agents which prime the neutrophil NADPH oxidase develop during routine storage of whole blood and packed red blood cells. This plasma priming activity can be inhibited by bepafant (WEB 2170), a specific platelet activating factor (PAF) receptor antagonist. Quantitation of the priming agent(s), by a commercially available radioimmunoassay for PAF, reproducibly demonstrated high levels of PAF activity. However, analysis of these plasma samples from stored blood components by gas chromatography/mass spectroscopy did not reveal any 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine. We conclude that the polyclonal antibody to PAF used in these studies may have recognized different epitopes of a family of heterogeneous, biologically active lipids that manifest their effects through the PAF receptor.

Azepines↗
PubMed1993

Quality control functions of the Visual Field Reading Center (VFRC) for the Optic Neuritis Treatment Trial (ONTT).

The Visual Field Reading Center (VFRC) was established to assess visual field testing in the Optic Neuritis Treatment Trial (ONTT), to train and certify ONTT technicians, and to monitor the quality of the visual fields through evaluation of the technical aspects of the visual field testing. We describe the functions of the VFRC personnel and the standardized test protocols developed by the VFRC for Humphrey and Goldmann perimetry. We also describe the VFRC procedures for training and certifying visual field technicians, double-checking the eligibility of ONTT patients, assessing the quality of the visual field data, and processing visual field data. In addition, we describe the principles applied by the director and associate director of the VFRC in their clinical classification of the various localized and diffuse visual field defects observed in the Humphrey and Goldmann visual fields. The VFRC has processed more than 14,000 Humphrey and Goldmann visual field tests. The visual field quality control procedures and visual field defect classification process have been shown to be quite reproducible. Through quality control assessment procedures, we have been able to pinpoint a variety of problems at an early stage and promptly implement corrective measures. The standardized test protocols, technician training and certification procedures, and quality control assessment techniques used by the VFRC for the ONTT may serve as a model for future clinical trials employing visual field data as an outcome measure. These procedures can also be used to enhance visual field reliability in ophthalmological practices.

Education↗
PubMed1993

Benzodiazepine effects on flicker sensitivity: role of stimulus frequency and size.

1. Benzodiazepines (BZDs) impair sensitivity to temporally modulated visual stimuli (flicker). Critical flicker-fusion frequency (CFF) is commonly used as a measure of this effect, but it only measures sensitivity to a narrow range of frequencies, usually above 25 Hz. Are other frequencies more sensitive to the effects of BZDs? 2. Flicker sensitivity at 1, 2, 4, 8, 16, and 32 Hz was measured for 1 degrees and 5 degrees stimuli before and 50 to 100 minutes after triazolam (0.25 mg), lorazepam (1.0 mg) and placebo. Drug effects on CFF were also measured. 3. Both BZDs significantly impaired overall flicker sensitivity. Triazolam produced 50% more impairment than lorazepam. CFF was significantly impaired by triazolam. BZD effects did not vary with stimulus size. 4. Significantly greater BZD-induced impairment of flicker sensitivity occurred at 16 Hz than at 1, 2, 4, or 32 Hz. 5. The magnitude of BZD effects on flicker sensitivity vary with the temporal frequency of the stimulus. BZD effects are greatest for 8-16 Hz stimuli.

Adult↗
PubMed1993

A prospective three-year study of response properties of normal subjects and patients during automated perimetry.

PURPOSE: The purpose of this study is to evaluate prospectively the reliability characteristics of patients undergoing automated perimetry over a 3-year period and compare these results with the results of previous investigations. METHODS: The subjects included 48 normal observers, 32 ocular hypertensive subjects, and 19 patients with early glaucomatous visual field loss. Both eyes were tested annually for 3 years with automated perimetry, using the standard procedures for the Humphrey Field Analyzer. Fixation losses, false-positive errors, false-negative errors, and short-term variability (double determinations) were evaluated. RESULTS: Short-term variability was slightly higher for the early glaucoma group than for the normal observer and ocular hypertensive groups, but there were no meaningful changes in short-term variability over 3 years. False-positive errors were very low in all three groups throughout the investigation. False-negative errors were slightly higher in the early glaucoma group, but all three groups had relatively low false-negative error rates throughout the study. Fixation losses were the most common source of unreliable results. The number of fixation losses decreased for the second and third years of the study. CONCLUSION: Contrary to a previous report, a relatively low number of unreliable tests were found for both initial and follow-up visits. The majority of unreliable visual field tests were sporadic events. Only a few subjects repeatedly produced unreliable test results. The authors conclude that automated perimetry can provide a reliable means of following patients over extended periods of time.

Adult↗