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Biomedical subjects

D Solomon

Publications and source records attributed to D Solomon.

At least 37 records · Page 2Linked to original sources

Validity of Listing's law during fixations, saccades, smooth pursuit eye movements, and blinks.

In its original formulation, Listing's law referred only to eye positions during steady fixation. In recent years, however, several studies have suggested that Listing's law can be extended to the movements of the eyes, including during saccades and smooth pursuit. A major problem in deciding whether or not Listing's law is obeyed during eye movements is the influence of any spontaneous fluctuations in torsional eye position. To try to settle this question, the three-dimensional position of the eyes (around the three axes: horizontal, vertical, and torsional) was recorded with dual search coils in five normal subjects during fixations, 20 degrees saccades, blinks, and 20 degrees pursuit movements with a 20 degrees/s stimulus velocity. Eye movements across a wide range of horizontal positions were measured at different elevations of gaze during 11 min. Variability (as reflected in the standard deviation of torsional eye position) was used as a measure of the validity of Listing's law. After linear detrending single trials, each lasting 21.5 s, to remove the effects of drift over minutes, the reduction in the standard deviation of torsional position in tertiary eye positions was 54% assuming a planar and 58% assuming a second-order curved Listing's surface. We attributed this long-term fluctuation of the torsional signal to slippage of the coil on the eye. The remaining variability was mainly due to short-term fluctuation of eye torsion over seconds. The impact of hysteresis, associated with consecutive centrifugal-centripetal horizontal movements, on the variability of torsional eye position appeared negligible. Peak increases in the standard deviation from the fixation baseline after fitting individual Listing's planes for each trial were 348% during blinks, 141% during saccades, and 72% during pursuit movements (median value of five subjects). In conclusion, Listing's law during blinks, saccades, and pursuit is less valid than during fixations, which raises doubts about the existence of an internal "Listing's law operator" for eye movements. Possibly, central eye velocity commands do not comply with Listing's law.

Blinking

Tracheal gas insufflation combined with high-frequency oscillatory ventilation.

OBJECTIVES: To determine the efficacy of tracheal insufflation delivered by two different catheter designs on CO2 elimination when used in conjunction with high-frequency oscillatory ventilation. DESIGN: A nonrandomized before and after trial. Each animal served as his own control. SUBJECTS: Ten mongrel dogs weighing 20.9 +/- 1.9 kg. Four animals were assigned to a normal lung group and six animals underwent lung injury by large volume saline lavage. INTERVENTION: Permissive hypercapnia was allowed to occur by selecting oscillator settings that would lead to alveolar hypoventilation. Proximal mean airway pressure was kept constant. Tracheal gas was insufflated at 1 cm above the carina for 30 min periods at gas flows of 5 to 15 L/min. MEASUREMENTS AND MAIN RESULTS: Carinal pressure, hemodynamic parameters (cardiac output, mean arterial pressure, pulmonary artery occlusion pressure), and gas exchange parameters (PaCO2, PaO2, PaO2/FIO2, shunt fraction, D O2) were measured. For the normal dogs, at catheter flow of 15 L/min; the forward thrust catheter increased carinal pressure and Pao2/FIO2 BY 30% (p<.003) and 105% (p<.005), respectively. The forward thrust catheter reduced Paco2 by 40% (p<.04). The reverse thrust catheter increased PaO2/FIO2 by 102% (p<.001) and decreased pressure and PaCO2 by 44% (p<.001) and 34% (p<.003), respectively. For the injured dogs, at catheter flow rate of 15 L/min, the forward thrust catheter increased carinal pressure, PaO2, and PaO2/FIO2 by 6% (p<.001), 23% (p<.001), and 24% (p<.02), respectively. The forward thrust catheter reduced PaCO2 by 29% (p<.002). The reverse thrust catheter increased PaO2 and PaO2/FIO2 both by 11% (p<.02) and reduced carinal pressure and PaCO2 by 23% (p<.001) and 18% (p<.002), respectively. CONCLUSIONS: Tracheal gas insufflation is capable of improving oxygenation and ventilation in acute lung injury when combined with high-frequency oscillatory ventilation. The addition of this second gas flow at the level of the carina raises or lowers distal airway pressure, the magnitude of which is dependent on the direction and rate of gas flow. The beneficial effects of tracheal gas insufflation may be tempered by the long-term effects of altering distal airway pressure; lowering distal airway pressure may lead to atelectasis, whereas raising distal airway pressure may lead to an auto-positive end-expiratory pressure (auto-PEEP) effect.

Animals

Importance of psychotic features to long-term course in major depressive disorder.

OBJECTIVE: Most efforts to describe the prognostic significance of psychotic features in depression have been limited to single assessments 1 year or less after the initial evaluation. However, the various biological and treatment response differences between patients with psychotic and nonpsychotic depression suggest that prognostic differences may be very long-term. METHOD: The 787 patients described here entered the study as they sought treatment at one of five academic medical centers; they had either RDC major depressive disorder or schizo-affective depression (other than the mainly schizophrenic subtype) and completed at least 6 months of follow-up. Of these, 144 (18.3%) had psychotic depression as defined here. Patients provided follow-up interviews at 6-month intervals for 5 years and annually thereafter; 98 of those with psychotic depression and 434 of those with non-psychotic depression were followed for 10 years. RESULTS: Those who began follow-up with psychotic depression had fewer weeks with minimal symptoms in each of the 10 years of follow-up and reported more psychosocial impairment at both 5 and 10 years. Both the index episode and the first recurrence of psychotic depression lasted longer than nonpsychotic episodes, but nonpsychotic episodes among previously psychotic individuals were relatively brief. Intervals between episodes were significantly shorter for patients who had ever been psychotic. CONCLUSIONS: Together with evidence that psychotic features are highly recurrent, these data show 1) that psychotic features denote a lifetime illness of greater severity and 2) that within individuals, psychotic features may emerge in only the more severe episodes.

Adult

Phase I crossover study of paclitaxel with r-verapamil in patients with metastatic breast cancer.

PURPOSE: We conducted a phase I crossover study of escalating doses of both paclitaxel (Taxol; Bristol-Myers, Squibb, Princeton, NJ) and r-verapamil, the less cardiotoxic stereoisomer, in heavily pretreated patients with metastatic breast cancer. PATIENTS AND METHODS: Twenty-nine patients refractory to paclitaxel by 3-hour infusion were treated orally with r-verapamil every 4 hours starting 24 hours before the same-dose 3-hour paclitaxel infusion and continuing for a total of 12 doses. Once the maximum-tolerated dose (MTD) of the combination was determined, seven additional patients who had not been treated with either drug were evaluated to determine whether the addition of r-verapamil altered the pharmacokinetics of paclitaxel. Consenting patients had tumor biopsies for P-glycoprotein (Pgp) expression before receiving paclitaxel and after becoming refractory to paclitaxel therapy. RESULTS: The MTD of the combination was 225 mg/m2 of r-verapamil every 4 hours with paclitaxel 200 mg/m2 by 3-hour infusion. Dose-limiting hypotension and bradycardia were observed in three of five patients treated at 250 mg/m2 r-verapamil. Fourteen patients received 32 cycles of r-verapamil at the MTD as outpatient therapy without developing cardiac toxicity. The median peak and trough serum verapamil concentrations at the MTD were 5.1 micromol/L (range, 1.9 to 6.3), respectively, which are within the range necessary for in vitro modulation of Pgp-mediated multidrug resistance (MDR). Increased serum verapamil concentrations and cardiac toxicity were observed more frequently in patients with elevated hepatic transaminases and bilirubin levels. Hematologic toxicity from combined paclitaxel and r-verapamil was significantly worse compared with the previous cycle of paclitxel without r-verapamil. In the pharmacokinetic analysis, r-verapamil delayed mean paclitaxel clearance and increased mean peak paclitaxel concentrations. CONCLUSION: r-Verapamil at 225 mg/m2 orally every 4 hours can be given safely with paclitaxel 200 mg/m2 by 3-hour infusion as outpatient therapy and is associated with serum levels considered active for Pgp inhibition. The addition of r-verapamil significantly alters the toxicity and pharmacokinetics of paclitaxel.

ATP Binding Cassette Transporter, Subfamily B, Mem

Continuous infusion of the anti-CD22 immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: a phase I study.

IgG-RFB4-SMPT-dgA consists of deglycosylated ricin A chain (dgA) coupled to the monoclonal antihuman CD22 antibody, RFB4. This study determined the maximally tolerated dose (MTD) of this immunotoxin (IT) administered as a continuous 8-day infusion to 18 patients with B-cell lymphoma (30% CD22+ tumor cells) over 8 days. The MTD was 19.2 mg/m2/192 h (maximum toxicity grade 1), with vascular leak syndrome (VLS) as dose-limiting toxicity (DLT) at 28.8 mg/m2/192 h (grades 3 through 5 in 7 of 11 patients). Predictors of severe VLS included serum IT concentrations greater than 1,000 ng/mL and the absence of circulating tumor cells. Decreased urine sodium excreted in 24 hours provided evidence for mild VLS without notable changes in serum albumin. Four partial responses, 3 minor responses, 6 stable disease, and 3 progression of disease were observed. The mean maximal serum concentration (Cmax) in initial courses at the MTD (19.2 mg/m2) was 443 +/- 144 ng/mL (n = 3; range, 326 to 604). At 28.8 mg/m2/192 h, the Cmax was highly variable (n = 11; mean, 1,102 +/- 702; range, 9.6 to 2,032 ng/mL). Human antimouse or antiricin antibodies developed in 6 of 16 (37.5%) patients after one course of IT. However, 10 eligible patients received multiple courses of IT. Changes in serum cytokines and cytokine receptors did not correlate with toxicity but decreased soluble interleukin-2 receptor concentrations correlated with clinical response. Comparison to a prior study with the same IT administered by intermittent bolus infusions (Amlot et al, Blood 82:2624, 1993) suggests similar clinical response, toxicity, and immunogenicity.

Adult

Transient torsion during and after saccades.

In five normal subjects, we analyzed uncalled for torsion (blips) during and after horizontal and vertical saccades. Torsion was defined as movement out of Listing's plane. During horizontal saccades in downward gaze the abducting eye extorted and the adducting eye intorted. The direction of the blips reversed in upward gaze. Peak torsional amplitudes (up to 1-2 deg) were always reached during saccades; drifts back to Listing's plane outlasted the saccades. Torsion of the extorting eye was larger than that of the intorting eye, producing a transient positive cyclovergence. Torsion and cyclovergence evoked by vertical saccades were also stereotyped in each eye, but showed idiosyncratic differences among subjects. We conclude that Listing's law is violated during saccades. Transient saccade-evoked torsion might reflect properties of the three-dimensional velocity-to-position integrator and/or the ocular plant.

Adult

Ultrasound-guided fine-needle aspiration of parathyroid lesions: a morphological and immunocytochemical approach.

Ultrasound-guided (US) fine-needle aspiration (FNA) can successfully localize abnormal parathyroid tissue (PT) preoperatively in hyperparathyroid patients. Samples from 12 patients with primary hyperparathyroidism evaluated using this technique since 1990 at the National Institutes of Health form the basis of this report. Eleven patients had undergone previous parathyroid surgery that failed to correct their hyperparathyroidism. Cytological evaluation and C-terminal (midmolecule) parathyroid hormone radioimmunoassay (PTH RIA) were performed on all samples. When sufficient material was available, immunocytochemical stains for chromogranin and thyroglobulin were performed. All cytological diagnoses were made with-out knowledge of the PTH RIA results. Using a combined approach of cytology and immunocytochemistry, six of 12 of the samples (50%) were diagnosed as PT. Follow-up on these six patients was confirmatory. Four of 12 samples (33%) were identified as thyroid; one of these patients had a PT adenoma identified in another location (the remaining three patients await further localization studies). Two of 12 samples (17%) could not be diagnosed because of insufficient cellularity; in both patients PT lesions were found in other locations. Morphological features of PT in FNA include the presence of cellular tissue fragments with epithelial cells arranged perivascularly around capillary cores, an overall organoid or trabecular architecture, and frequent microacini. Parathyroid tissue cells have round, fairly uniform nuclei measuring 6 to 8 microns. Clusters of larger oxyphil cells may show considerable anisonucleosis. The absence of features of thyroid tissue such as hemosiderin-laden macrophages, abundant colloid, and paravacuolar granules is significant. However, in cases of intrathyroidal PT, admixed thyroid material included in the aspiration tract may be present immunocytochemical stains for chromogranin, which is present in parathyroid tissue but not thyroid follicular cells, were positive in six of six samples interpreted as PT by cytology. No thyroglobulin staining was observed in any of the four of six PT samples for which material was available. C-terminal (midmolecule) PTH RIA correlated with cytological diagnoses in 100% of samples. Parathyroid hormone levels ranged from 1,300 to 262,000 pg/mL (normal blood level, 50 to 340 pg/mL) in the six samples diagnosed as PT by cytology. Parathyroid hormone RIA levels in the six non-PT samples were below normal blood values. The combined approach of cytology and immunocytochemistry provides high diagnostic accuracy in the interpretation of US-guided FNA for preoperative localization of parathyroid tissue.

Adult

Interleukin-10 in the vitreous of patients with primary intraocular lymphoma.

PURPOSE: To find an accurate and simple method to diagnose primary intraocular lymphoma. METHODS: We prospectively analyzed concentrations of interleukin-10, interleukin-1, interleukin-2, interleukin-4, and interleukin-6 in vitrectomy specimens from three patients with primary intraocular lymphoma and five patients with uveitis by enzyme-linked immunosorbent assay. RESULTS: Interleukin-10 in the vitreous was detected in patients with primary intraocular lymphoma. Interleukin-10 levels correlated with clinical activity and the number of malignant cells. CONCLUSION: Concentrations of interleukin-10 in the vitreous may be a helpful clue to both clinicians and pathologists in diagnosing primary intraocular lymphoma.

Enzyme-Linked Immunosorbent Assay

Characterization of the renal pathology of a familial form of renal cell carcinoma associated with von Hippel-Lindau disease: clinical and molecular genetic implications.

We examined 12 patients with von Hippel-Lindau disease and renal cell carcinoma to characterize the pathological findings after renal surgery (total 161 lesions). Tissue from 15 partial nephrectomies and 1 radical nephrectomy was obtained for examination. Pathological evaluation identified 116 cystic lesions, 25 of which (21%) were malignant, and 45 solid lesions, 41 of which (91%) were renal cell carcinoma. Each kidney had a mean of 7.8 cystic and 3.0 solid lesions. Of 66 malignant lesions 35 (53%) were comprised of cells with only clear cell cytological features and 30 (45.5%) contained predominantly clear cells with scattered granular cells. One malignant lesion (1.5%) contained sarcomatoid renal cell carcinoma with clear and granular cells. Microscopic invasion of the pseudocapsule was common (13 of 25 clinically cystic tumors [52%] and 31 of 41 clinically solid lesions [76%]) but no tumor extended through the pseudocapsule. All lesions without a pseudocapsule were well circumscribed. Our study establishes the clear cell cytological features as the primary finding observed in patients with von Hippel-Lindau disease. Many cystic lesions contained renal cancer, demonstrating the need for removal of all cystic lesions when this can be safely performed. The well circumscribed nature of the tumors lends them to parenchymal sparing procedures.

Adult

Characteristics and significance of untreated major depressive disorder.

OBJECTIVE: This study sought to describe the characteristics and consequences of untreated major depressive disorder. METHOD: As part of a family study of probands with major affective disorders, raters assessed 3,119 first-degree relatives, spouses, and comparison subjects. When 2,237 (71.7%) of these individuals were reassessed 6 years later, 547 had experienced episodes of major depressive disorder in the interval. Those who had sought any form of treatment for any episode of major depressive disorder in the interval were compared, by baseline demographic characteristics and clinical features of their worst episodes of major depressive disorder, to those who had not. Individuals who had had untreated major depressive disorder were then compared, by changes in socioeconomic status and by levels of psychosocial impairment at follow-up, to a matched group with no major depressive disorder in the interval. RESULTS: The worst episodes of 313 treated individuals, compared to those of 234 untreated individuals, were characterized by older age, symptoms of the endogenous subtype, longer durations, and the presence of disruption in role function. Each of these factors contributed independently to the distinction between treated and untreated episodes. Untreated individuals experienced significant psychosocial impairment on follow-up but did not show the economic disadvantages shown elsewhere for probands who began follow-up as they sought treatment at tertiary medical centers. CONCLUSIONS: These data suggest that illness characteristics and age determine the decision to seek treatment for major depressive disorder. Untreated depression is apparently associated with long-standing psychosocial difficulties but not with serious economic consequences.

Adolescent

Possible mechanisms for horizontal gaze deviation and lateropulsion in the lateral medullary syndrome.

We report a patient who developed conjugate horizontal gaze deviation and ipsipulsion of saccades from a lateral medullary infarction. Recent evidence suggests that the gaze deviation may result from increased inhibition of the ipsilateral vestibular nucleus and ipsipulsion of saccades from decreased excitation of the contralateral ocular premotor areas of the brainstem reticular formation. Interruption of the olivocerebellar pathways may account for both of these ocular motor abnormalities.

Adult

Cyclodeviation in skew deviation.

We examined four patients with dorsolateral pontomedullary lesions and skew deviation, with ocular torsion of varying symmetry. In three patients, the hypotropic eye was excyclodeviated relative to the fellow eye. Observations of these patients, combined with recent evidence, suggest that cyclodeviation is a frequent component of skew deviation and may result from variable involvement of utricular, semicircular canal, and cerebelloocular pathways. Although cyclodeviation is a feature of trochlear-nerve palsies, its presence does not exclude skew deviation and underlying brainstem lesions.

Adult

Stimulation of the nodulus and uvula discharges velocity storage in the vestibulo-ocular reflex.

The nodulus and sublobule d of the uvula of rhesus and cynomolgus monkeys were electrically stimulated with short trains of pulses to study changes in horizontal slow-phase eye velocity. Nodulus and uvula stimulation produced a rapid decline in horizontal slow phase velocity, one aspect of the spatial reorientation of the axis of eye rotation that occurs when the head is tilted with regard to gravity during per- and post-rotatory nystagmus and optokinetic after-nystagmus (OKAN). Nodulus and uvula stimulation also reproduced the reduction of the horizontal time constant of post-rotatory nystagmus and OKAN that occurs during visual suppression. The brief electric stimuli (4-5 s) induced little slow-phase velocity and had no effect on the initial jump in eye velocity at the onset or the end of angular rotation. Effects of stimulation were unilateral, suggesting specificity of the output pathways. Activation of more caudal sites in the uvula produced nystagmus with a rapid rise in eye velocity, but the effects did not outlast the stimulus and did not affect VOR or OKAN time constants. Thus, stimulation of caudal parts of the uvula did not affect eye velocity produced by velocity storage. We postulate that the nodulus and sublobule d of the uvula control the time constant of the yaw axis (horizontal) component of slow-phase eye velocity produced by velocity storage.

Animals

Diagnosis of pulmonary microvascular metastases by cytologic evaluation of pulmonary artery catheter-derived blood specimens.

Pulmonary microvascular tumor embolization is a recognized cause of respiratory distress in cancer patients that is rarely diagnosed antemortem. Previous studies with relatively few patients have reported high diagnostic yield using wedged pulmonary artery catheter-derived blood samples to evaluate dyspneic cancer patients for possible microembolization. From 1991 to 1993, 21 cancer patients with respiratory distress of relatively acute onset and varying severity who required pulmonary artery catheterization for hemodynamic monitoring were evaluated using this technique. Pulmonary microvascular cytology (PMC) was interpreted as positive for malignant cells in nine of 21 patients presenting with a range of tumor types, including carcinomas of the breast, colon, and pancreas as well as non-Hodgkin's lymphoma. In 11 patients the PMC was interpreted as negative. One case was considered nondiagnostic. Megakaryocytes, noted in most PMC specimens as well as in several samples of simultaneously drawn peripheral blood, may mimic epithelial tumor cells. Immunocytochemical stains for factor VIII and cytokeratins were used to resolve occasional diagnostic dilemmas. Clinical and/or pathologic follow-up information was available for all patients. Diagnostic accuracy was highest for epithelial malignancies. Two false-negative results occurred in patients with metastatic choriocarcinoma and breast carcinoma. Circulating malignant cells in the peripheral blood of a patient with non-Hodgkin's lymphoma led to one false-positive diagnosis. Benign lymphoid elements in PMC generally have a reactive and variable appearance that should not be misinterpreted as lymphoma. We conclude that PMC is a useful tool in the evaluation of dyspneic cancer patients requiring pulmonary artery catheterization for hemodynamic monitoring and its use potentially avoids additional diagnostic procedures.

Catheterization, Peripheral

Case report: rectal stenosis due to extramedullary haemopoiesis--radiological features.

Although extramedullary haemopoiesis (EMH) is relatively common in myelofibrosis, it is seldom symptomatic and rarely involves the intestinal tract. We report a case in which perirectal infiltrate resulted in clinically symptomatic constipation. The barium enema showed tubular rectal narrowing with mucosal pleating. On computed tomography a poorly marginated soft tissue mass was shown to be replacing the perirectal fat.

Aged