Biomedical subjects
Publications and source records attributed to W A Fletcher.
The authors describe unusual magnetic resonance findings due to carbon monoxide poisoning in a 34-year-old woman. With T2-weighted imaging, increased signal intensity was observed bilaterally in the putamen and the caudate nucleus. Lesions of high signal intensity in the globus pallidus, which have been previously reported, were also observed.
The pore size and the in vivo behaviour of four poly(2-hydroxyethyl methacrylate) sponges were investigated. The sponges were synthesized by polymerization of monomer in 70, 80 and 90 wt% water, respectively. In one of the formulations, a high amount of initiator was added. The average pore diameter was calculated with Ferry's equation and the results compared to those obtained by examination of samples using environmental scanning electron microscopy. The use of the equation greatly underestimated the size of pores. We also showed that the pores in polymers obtained in 70 wt% water were not interconnected, whilst the pores in polymers obtained in 80 and 90 wt% water, respectively, were larger and interconnected throughout the polymer. When implanted subcutaneously in rabbits, only the latter polymers allowed invasion and proliferation of cells. Penetration and proliferation of cells in these sponges were also assessed by an in vitro method using cultured human fibroblasts. The procedure included the overlaying of a glass plate covered by confluent cultured cells on to the surface of polymer impregnated with collagen. The depth of migration and number of sections needed to be cut to count a fixed number of invading cells were measured after incubation for 2 wk and used as indicators in comparing the ability of various sponges to allow cellular invasion. The assay showed that more cells invaded a hydrogel sponge produced in 80 wt% water than one produced in 90 wt% water. It also showed that the cut polymer surfaces allowed a greater cellular invasion than the moulded ones.
1. We studied saccades to briefly flashed targets in 8 human subjects. The target flash occurred (i) during smooth pursuit ("ramp-flash"), (ii) just before a saccade to another target ("step-flash"), or (iii) during steady fixation ("flash only"). All lights were extinguished after the target flash so that smooth pursuit or saccadic eye movements occurred during the interval of complete darkness between the target flash and the saccade to it. We compared these saccades to those made without intervening eye movement (flash only), and quantified the extent to which the saccadic system compensated for the change in eye position that occurred during the dark interval. 2. Saccades to control flashes were reasonably accurate (mean gain 0.87) and consistent. Compensation for the intervening eye movement in the ramp-flash and step-flash paradigms was highly variable from trial to trial. On average, subjects compensated for 27% of the intervening pursuit eye movement on ramp-flash trials and for 58% of intervening saccadic movement on step-flash trials. 3. Multiple regression analysis showed that the variability did not depend on factors such as variations in underlying saccadic gain, response latency, timing of stimuli or size of the required response. We conclude that this variability is intrinsic to saccadic responses that require the use of an eye position signal. 4. These results show that an eye position signal is available to the saccadic system but that this signal has low fidelity.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunohistochemical studies of human breast cancers using human milk fat globule (HMFG) antibodies are divergent regarding the association with histologic differentiation. To clarify this association 392 tumors were assessed using two antibodies, HMFG-1 and HMFG-2. In half the tumors studied the tissue reaction to both antibodies was the same and in 63% the site of reaction was identical. Using both univariate and multivariate statistics, a highly significant association was recorded between membrane staining and well differentiated cancers and cytoplasmic staining and poor differentiation. Well differentiated tumors contained significantly more reactive cells. Complementing these findings was the association between age at diagnosis, tumor stage, and estrogen receptor status and differentiation. It is possible that immunohistochemical analysis with HMFG antibodies will provide better characterization of tumor differentiation than morphologic interpretation.
The status of axillary lymph nodes in patients with breast cancer is important prognostically but does not identify all patients who will have long or short survival. To determine if the immunohistochemical reaction of tumor cells to human milk fat globule (HMFG) antibodies will define prognosis more specifically, we examined patients with node-negative disease and patients with more than three positive nodes, the extremes of the prognostic spectrum. In both node-negative and node-positive groups, patients who relapsed were matched by age at diagnosis, tumor size, histologic type, and receptor status, with patients who remained disease-free for a minimum of 48 months. Patients with poor survival had a higher proportion of poorly differentiated cancers. The ability to generate antigens recognized by HMFG antibodies was decreased in patients with recurrent disease, but this was significant only in patients with node-positive tumors. Tumors of patients who remained disease-free were more likely to have a pattern of membrane staining, while cytoplasmic staining was more frequent in those who relapsed. The results suggest that immunohistologic response to HMFG antibodies may assist in identifying cancers with poor prognosis, supplementing the prediction derived from node status.
Because postoperative radiation reduces chest wall metastasis after mastectomy, it is important to identify patients in whom it might develop. Pathologic and immunohistochemical features in 59 patients with chest wall metastasis were compared with characteristics in disease-free patients and patients with systemic metastases without chest wall metastasis. Immunohistochemical studies with human milk-fat globule (HMFG)-2 were not predictive, but a membrane reaction with HMFG-1 was associated with fewer systemic metastases and tumors, in which most of the cells reacted with the antibody had significantly decreased likelihood of chest wall metastasis. Antigenic concordance between the primary breast cancer and the chest wall metastasis was demonstrated. Neither tumor size nor axillary node metastasis predicted development of chest wall metastasis, but systemic metastases were less common when fewer than four nodes were involved, the primary tumor was well differentiated, and estrogen receptors were positive.
A tendency to reduce the use of benzophenone absorbers is currently evident in the manufacture of the UV-absorbing IOLs, mainly because the cutoff wavelengths are inferior to those provided by benzotriazoles. In principle, by incorporating large amounts of benzophenones it may be possible to achieve high cutoff wavelengths. A covalently bondable benzophenone UV absorber, Cyasorb UV-2098, was incorporated in poly(2-hydroxyethyl methacrylate) (PHEMA) in increasing concentrations, and certain associated phenomena were investigated. At 4% w/w absorber content, the nonhydrated polymers turned partially opaque. In water-swollen hydrogels, opacification occurred at a lower absorber content (2% w/w). By using extraction techniques and gas chromatography, we also found that up to 8% w/w of the absorber remained unpolymerized and could leach out from any material containing less than 5% w/w absorber. In samples with higher initial content of absorber, the amount of unreacted, leachable absorber was significantly higher (25% to 30%). Based on this study model (hydrogel/Cyasorb UV-2098), we concluded that benzophenone absorbers cannot provide cutoff wavelengths higher than those provided by benzotriazoles.
The clinical, histologic, and immunohistologic characteristics of 19 synchronous and 47 metachronous bilateral breast cancers was compared. Patients with metachronous tumors were 5 years younger and more likely to have a family history of breast cancer than those patients with synchronous cancers. The nondominant synchronous cancer was usually discovered mammographically accounting for small, node-negative tumors, and high prevalence of in situ lesions. The same was true of the second metachronous tumor when discovered mammographically. Patients with metachronous cancers who were not in a follow-up program had second cancers with characteristics similar to incidentally diagnosed unilateral cancer. The mean interval between metachronous cancers was 101 months. Significantly more first metachronous tumors were invasive lobular cancers. Histologic type of the first and second tumor was the same in only 68% of synchronous and 61% of metachronous cancers. Combined histologic evidence and differentiation was concordant in only 13% and 22% of tumors, respectively. Immunoperoxidase studies were performed with two human milk fat globule antibodies. Each antibody reacted similarly in the first and second tumor in less than 50% of tumors and concordance was less than 25% when both antibody reactions were assessed. Differences in histologic evidence, differentiation, and immunohistologic reaction suggest that both synchronous and metachronous cancers are morphologically and functionally dissimilar.
In four normal human subjects we measured eye movements during full-field optokinetic stimulation (10-220 deg/s) and determined the relationship among retinal-slip velocity (drum velocity minus slow-phase eye velocity), the slow-phase velocity of optokinetic nystagmus (OKN) and the initial value of the slow-phase velocity of optokinetic afternystagmus (OKAN) measured in darkness. OKN and OKAN were maximum (63-84 and 11-19 deg/s, respectively) when retinal slip ranged from 30-100 deg/s. For higher values of retinal slip, OKN and OKAN fell (in 3 subjects) or reached a plateau (in the fourth). The amplitude of OKAN in human beings was much less than that reported in monkeys. The shape, however, of the curve relating retinal slip to the amplitude of OKAN was similar to that of monkeys. Furthermore, in both cases the curve resembles that obtained by plotting the results of experimental recordings of neural discharge in the nucleus of the optic tract as a function of retinal slip. These results imply that the processing of visual information for generation of OKAN is similar in monkeys and human beings but that the gain of the system is much less in human beings. We also found that fixation of a small target during optokinetic stimulation nearly completely prevented the development of OKAN while fixation of a small target for short periods after optokinetic stimulation did not alter the pattern of decay of OKAN. Thus, fixation may actively prevent the coupling of visual information into the velocity-storage mechanism.
We examined seven patients who had a syndrome of symptomatic monocular blind spot enlargement without optic disc edema. Two patients had previous blind spot enlargement that resolved over several months. The scotoma in each patients was absolute, measured 15 degrees to 20 degrees in diameter, had steep geographic margins, and extended to within 5 degrees to 10 degrees of fixation. Typically, patients had normal visual acuity, color vision, pupillary responses, and ophthalmoscopic findings. Photostress recovery, tested in two patients, was prolonged in the affected eye. Fluorescein angiography showed no abnormalities corresponding to the scotoma. Orbital computed tomographic scans in three patients and visual evoked responses in one patient were normal. Multifocal electroretinography, performed in two patients, showed loss of retinal waveforms in a large region surrounding the optic disc. Our findings suggest that retinal dysfunction produces this big blind spot syndrome, but we do not know its cause.
Upward and downward gaze palsy was measured by a magnetic search coil technique and correlated with neuropathologic findings in a patient with a unilateral midbrain infarct. Oculography demonstrated (1) saccadic palsy above primary position and slow, limited vertical saccades below; (2) low-gain, restricted vertical pursuit; and (3) low-gain, abnormal phase lead, and restricted range of the vertical vestibulo-ocular reflex (VOR). Bidirectional palsy of vertical saccades is attributed to unilateral loss of burst cells in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and interruption of burst cell fibers from the opposite riMLF. Pathways mediating vertical pursuit and integration of the vertical VOR also traversed the infarct, which included the interstitial nucleus of Cajal.
A 24-year-old man with recent-onset seizures was found to have an occipital lobe ganglioglioma with homonymous quadrantanopia and trans-synaptic atrophy of retinal nerve fibers. This association indicates that gangliogliomas may arise during neural development and exist for many years before onset of symptoms.
Electrophysiologic studies were carried out on 11 patients with Holmes-Adie syndrome, 8 of whom had reduced or absent ankle jerks. Conduction velocities and evoked nerve and muscle compound action potentials in the peroneal, posterior tibial, and sural nerves were normal. The H reflex was absent (or virtually absent) in the patients with depressed reflexes. The amplitude of the composite Ia EPSP in single soleus motoneurons was estimated from changes in firing probability of voluntarily activated soleus motor units in response to stimulation of low threshold afferents in the tibial nerve. These amplitudes were used to test the afferent side of the reflex pathway. Composite group Ia EPSPs in Holmes-Aide patients with hyporeflexia were smaller than normal or absent, indicating that the areflexia in the Holmes-Aide syndrome is due to loss of large spindle afferents or reduced effectiveness of their monosynaptic connections to motoneurons.
Smooth ocular pursuit was measured by magnetic search coil oculography in 13 patients with Alzheimer's disease and compared with control subjects. Smooth eye movement gain was uniformly reduced in Alzheimer's disease at all target velocities for several frequencies of sinusoidal target motion, signifying impairment of steady-state gain. Normal phase relationships between the target and eyes indicated an intact predictor mechanism for smooth pursuit. When peak target velocity was held constant, pursuit gain decreased markedly in response to small increments of target acceleration, indicating involvement of an acceleration saturating nonlinear element that limits smooth pursuit. Large-amplitude saccadic intrusions, in the direction of target motion, often disrupted pursuit; smooth eye movements continued in response to target velocity despite large position errors of the fovea from its target. These disorders of smooth eye movement control can quantify motor dysfunction in Alzheimer's disease.
Aneurysms of the intracavernous portion of the internal carotid artery may become very large, but they very rarely rupture. A case is described in which rupture of such a lesion resulted in a lethal massive subdural hematoma with transtentorial herniation. This is the second reported case of substantiated intracranial rupture from a wholly intracavernous carotid artery aneurysm.
Smooth pursuit was studied during predictable L-dopa dose-related "off" periods of morning akinesia and wearing off and during "on" periods in eight patients with idiopathic Parkinson's disease. Smooth pursuit gain was significantly reduced in patients during both on and off phases. Despite marked fluctuations between parkinsonism and periods of near normal skeletal motion, there were no changes in smooth pursuit gain. We conclude that unvarying paresis of smooth pursuit in Parkinson's disease signifies involvement of neural circuits that are distinct from the dopaminergic mechanisms that mediate the on-off phenomenon of somatic motor control.
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High-frequency ventilation has been used successfully to manage life-threatening complications in premature infants with lung disease. Here we report a preliminary assessment of the efficacy and safety of high-frequency oscillatory ventilation-(HFO-A, A = active expiratory phase) when used as a primary ventilator in 11 infants of 24-34 weeks gestation who required ventilatory support. HFO-A was initiated after no more than 5.5 hr of conventional mechanical ventilation (CMV). HFO-A at 15 Hz was used for 12-203 hr following a protocol designed for rapid reduction of FI02 requirements. CO2 elimination was easily achieved in all infants. Oxygenation was satisfactory, except in one infant with congenital pneumonia. There were four deaths during HFO-A: two pulmonary (one congenital pneumonia; one pulmonary hemorrhage) and two nonpulmonary. The HFO-A protocol utilized lung volume recruitment maneuvers plus mean airway pressures (MAwP) greater than those generally used early in the course of CMV. Therefore, in a subset of infants less than or equal to 29 weeks' gestation with respiratory distress syndrome (RDS), ventilator pressures and gas exchange were compared in infants treated with either HFO-A or CMV. Maximum MAwP levels were reached earlier in six infants on HFO-A (5.2 +/- 2.5 hr; mean +/- SD) than in a comparable group of 9 CMV-treated infants (36 +/- 1 hr). This earlier use of high MAwP lowered the FI02 to less than 0.4 by 18.9 +/- 11 hr with HFO-A as compared with 64 +/- 6 hr using CMV, without any evidence of an increase in pulmonary complications. There were 17 complications in the nine CMV-treated infants; and four in the six HFO-A treated ones. We conclude that HFO-A, instituted early and used with a protocol designed for early reduction in FI02 requirements, demonstrates sufficient efficacy and safety to warrant further clinical trials in the routine management of infant RDS.