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Biomedical subjects

D Solomon

Publications and source records attributed to D Solomon.

At least 73 records · Page 4Linked to original sources

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↗

PAPNET analysis of reportedly negative smears preceding the diagnosis of a high-grade squamous intraepithelial lesion or carcinoma.

One hundred fourteen cervical smears obtained from 18 women developing biopsy-proven high-grade squamous intraepithelial lesions and two with invasive squamous carcinomas were analyzed by two pathologists using the PAPNET neural network-based automated screening system (PAPNET Analyses A and B). The smears were originally reported as negative and had been previously rescreened and reclassified according to The Bethesda System. Using the PAPNET video displays of 128 potentially abnormal cellular images per smear, each reviewer (PAPNET A and B) determined whether a smear required conventional rescreening. Results of the PAPNET triage were compared with the reclassification diagnoses of the smears by conventional microscopy. PAPNET Analysis A selected eight (14%) smears reclassified as negative, 25 (69%) as atypical squamous cells of undetermined significance, and 15 (71%) as squamous intraepithelial lesions (SIL) for rescreening. In PAPNET Analysis A, two (10%) SILs were not selected for rescreening, and four (19%) were considered unsatisfactory for analysis. PAPNET Analysis B selected 21 (37%) smears reclassified as negative, 25 (69%) as atypical squamous cells of undetermined significance, and 18 (86%) as SIL for review. In PAPNET Analysis B, two (10%) SILs were missed, and one (5%) smear was unsatisfactory for analysis. Each PAPNET analysis selected smears for rescreening in 19 (95%) of 20 patients and detected SILs in 10 patients that were missed in the original screening. Using PAPNET, SILs would have been detected a median of 56 months (PAPNET A) and 62 months (PAPNET B) before their actual discovery. These preliminary data suggest that PAPNET may help detect SILs missed in routine cytologic screening.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell↗

Immunocytochemical staining of vitreous cells. Indications, techniques, and results.

Diagnostic vitrectomy is often performed because of suspected infection or malignancy. Giemsa, Gram, and Papanicolaou stains are used routinely to identify the components in the vitreous. Immunocytochemical staining of cellular components of vitreous specimens has the potential to significantly increase the amount of useful information that can be gained from histopathologic study. Vitreous specimens from 14 patients undergoing diagnostic or therapeutic vitrectomy for infection, suspected primary intraocular lymphoma, or uveitis were examined by immunocytochemical staining using monoclonal antibodies specific for leukocyte subclass antigens and immunoglobulin. The three classes of disorders showed characteristic patterns of staining, which were useful in confirming microbiologic and clinical diagnoses. Infections showed more pronounced neutrophils and macrophages, primary intraocular lymphomas demonstrated light chain restriction of the malignant B lymphocytes, and uveitis was characterized by the predominance of T lymphocytes. The routine use of immunocytochemical staining is recommended to characterize cellular infiltrates and increase the diagnostic yield from vitrectomy specimens.

Antibodies, Monoclonal↗

Characterization of lymphocytes infiltrating human breast cancer: specific immune reactivity detected by measuring cytokine secretion.

Primary breast cancers from 19 patients and draining lymph nodes from nine of them (seven containing metastatic tumor) were used in growing tumor-infiltrating lymphocytes (TIL) in culture. TIL were studied for proliferation, phenotype, cytotoxicity, and the ability to secrete cytokines in response to autologous tumor. Lymphocytes from primary breast tumors proliferated in 15 of 19 cultures, a median of 6.7 x 10(3)-fold in 65 days. For eight of nine patients, lymphocytes derived from draining lymph nodes proliferated in culture, a median of 110-fold in 49 days. Breast TIL became predominantly CD4+ cells over time in culture and were 73% CD4+ and 21% CD8+ (means) at 63 days (median). Lymph node lymphocytes were 63% CD4+ at 51 days. TIL were poorly lytic in 4-hour 51Cr release assays. Lysis of autologous tumor occurred in only one of 12 breast TIL and one of nine lymph node cultures. This lysis was low (15% at effector:target = 40:1) and was nonspecific (non-major-histocompatibility-complex restricted). Cytokine secretion was tested by co-culturing TIL with autologous or allogeneic tumors for 24 hours. Cytokines were measured in culture supernatants by enzyme-linked immunosorbent assay or radioimmunoassay. TIL from three of 11 patients specifically secreted granulocyte macrophage-colony-stimulating factor, tumor necrosis factor-alpha and interferon-gamma when stimulated by autologous tumor and not by a panel of four to five allogeneic breast cancers. Cytokine secretion has made possible the identification of lymphocytes infiltrating breast cancers with specific immune reactivity. This finding will guide the development of new immunotherapies for patients with breast cancer.

Breast Neoplasms↗

Vestibuloocular reflex of rhesus monkeys after spaceflight.

The vestibuloocular reflex (VOR) of two rhesus monkeys was recorded before and after 14 days of spaceflight. The gain (eye velocity/head velocity) of the horizontal VOR, tested 15 and 18 h after landing, was approximately equal to preflight values. The dominant time constant of the animal tested 15 h after landing was equivalent to that before flight. During nystagmus induced by off-vertical axis rotation (OVAR), the latency, rising time constant, steady-state eye velocity, and phase of modulation in eye velocity and eye position with respect to head position were similar in both monkeys before and after flight. There were changes in the amplitude of modulation of horizontal eye velocity during steady-state OVAR and in the ability to discharge stored activity rapidly by tilting during postrotatory nystagmus (tilt dumping) after flight: OVAR modulations were larger, and tilt dumping was lost in the one animal tested on the day of landing and for several days thereafter. If the gain and time constant of the horizontal VOR change in microgravity, they must revert to normal soon after landing. The changes that were observed suggest that adaptation to microgravity had caused alterations in way that the central nervous system processes otolith input.

Animals↗

Stabilization of gaze during circular locomotion in light. I. Compensatory head and eye nystagmus in the running monkey.

1. A rhesus and cynomolgus monkey were trained to run around the perimeter of a circular platform in light. We call this "circular locomotion" because forward motion had an angular component. Head and body velocity in space were recorded with angular rate sensors and eye movements with electrooculography (EOG). From these measurements we derived signals related to the angular velocity of the eyes in the head (Eh), of the head on the body (Hb), of gaze on the body (Gb), of the body in space (Bs), of gaze in space (Gs), and of the gain of gaze (Gb/Bs). 2. The monkeys had continuous compensatory nystagmus of the head and eyes while running, which stabilized Gs during the slow phases. The eyes established and maintained compensatory gaze velocities at the beginning and end of the slow phases. The head contributed to gaze velocity during the middle of the slow phases. Slow phase Gb was as high as 250 degrees/s, and targets were fixed for gaze angles as large as 90-140 degrees. 3. Properties of the visual surround affected both the gain and strategy of gaze compensation in the one monkey tested. Gains of Eh ranged from 0.3 to 1.1 during compensatory gaze nystagmus. Gains of Hb varied around 0.3 (0.2-0.7), building to a maximum as Eh dropped while running past sectors of interest. Consistent with predictions, gaze gains varied from below to above unity, when translational and angular body movements with regard to the target were in opposite or the same directions, respectively. 4. Gaze moved in saccadic shifts in the direction of running during quick phases. Most head quick phases were small, and at times the head only paused during an eye quick phase. Eye quick phases were larger, ranging up to 60 degrees. This is larger than quick phases during passive rotation or saccades made with the head fixed. 5. These data indicate that head and eye nystagmus are natural phenomena that support gaze compensation during locomotion. Despite differential utilization of the head and eyes in various conditions, Gb compensated for Bs. There are various frames of reference in which an estimate of angular velocity that drives the head and eyes could be based. We infer that body in space velocity (Bs) is likely to be represented centrally to provide this signal.

Adaptation, Physiological↗

Stabilization of gaze during circular locomotion in darkness. II. Contribution of velocity storage to compensatory eye and head nystagmus in the running monkey.

1. Yaw eye in head (Eh) and head on body velocities (Hb) were measured in two monkeys that ran around the perimeter of a circular platform in darkness. The platform was stationary or could be counterrotated to reduce body velocity in space (Bs) while increasing gait velocity on the platform (Bp). The animals were also rotated while seated in a primate chair at eccentric locations to provide linear and angular accelerations similar to those experienced while running. 2. Both animals had head and eye nystagmus while running in darkness during which slow phase gaze velocity on the body (Gb) partially compensated for body velocity in space (Bs). The eyes, driven by the vestibuloocular reflex (VOR), supplied high-frequency characteristics, bringing Gb up to compensatory levels at the beginning and end of the slow phases. The head provided substantial gaze compensation during the slow phases, probably through the vestibulocollic reflex (VCR). Synchronous eye and head quick phases moved gaze in the direction of running. Head movements occurred consistently only when animals were running. This indicates that active body and limb motion may be essential for inducing the head-eye gaze synergy. 3. Gaze compensation was good when running in both directions in one animal and in one direction in the other animal. The animals had long VOR time constants in these directions. The VOR time constant was short to one side in one animal, and it had poor gaze compensation in this direction. Postlocomotory nystagmus was weaker after running in directions with a long VOR time constant than when the animals were passively rotated in darkness. We infer that velocity storage in the vestibular system had been activated to produce continuous Eh and Hb during running and to counteract postrotatory afterresponses. 4. Continuous compensatory gaze nystagmus was not produced by passive eccentric rotation with the head stabilized or free. This indicates that an aspect of active locomotion, most likely somatosensory feedback, was responsible for activating velocity storage. 5. Nystagmus was compared when an animal ran in darkness and in light. the beat frequency of eye and head nystagmus was lower, and the quick phases were larger in darkness. The duration of head and eye quick phases covaried. Eye quick phases were larger when animals ran in darkness than when they were passively rotated. The maximum velocity and duration of eye quick phases were the same in both conditions. 6. The platform was counterrotated under one monkey in darkness while it ran in the direction of its long vestibular time constant.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

Diagnosis of Pneumocystis carinii pneumonia by multiple lobe, site-directed bronchoalveolar lavage with immunofluorescent monoclonal antibody staining in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis.

The yields of both induced sputum examination and bronchoalveolar lavage (BAL) have been reported to be decreased for breakthrough episodes of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis. This study assessed whether the yield of a single middle or lower lobe BAL could be increased by the utilization of two techniques: (1) indirect immunofluorescent staining with a combination of two murine monoclonal anti-Pneumocystis antibodies in addition to routine toluidine blue O and cytopathologic staining, and (2) the performance of multiple lobe, site-directed BAL (i.e., both upper lobe and middle or lower lobe lavage, including the lobe with the greatest radiographic abnormality). Results of 252 fiberoptic bronchoscopies performed at the National Institutes of Health and the Los Angeles County-University of Southern California Medical Center were analyzed. P. carinii pneumonia was documented in 21 episodes in patients who did not receive prior anti-Pneumocystis chemoprophylaxis and in 41 episodes in patients who received aerosolized pentamidine. Monoclonal antibody staining and multiple lobe, site-directed BAL resulted in similar diagnostic yields for P. carinii in the nonprophylaxis (100%) and aerosolized pentamidine (98%) groups. If BAL had been performed without monoclonal antibody staining and multiple lobe, site-directed lavage, then the yield would have decreased to 95% in the nonprophylaxis group and to 80% in the aerosolized pentamidine group.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

A prospective study of the value of core needle biopsy and fine needle aspiration in the diagnosis of soft tissue masses.

We prospectively sampled 38 large soft tissue masses in 37 patients with both core needle biopsy (CNBX) and fine-needle aspiration (FNA) to determine the diagnostic utility of these biopsy methods. In 27 cases the histologic diagnosis made from the resected specimen was compared with the diagnosis based on the biopsy. CNBX correctly identified 16 of 16 malignant sarcomas and 10 of 11 benign masses (one was indeterminate). The grade of the sarcoma was determined correctly in every case. There were no false malignant or false benign CNBX diagnoses. FNA correctly classified 12 of 14 malignant sarcomas and four of 11 benign lesions. Diagnoses based on FNA were limited by a high proportion of samples, especially from benign lesions, that were inadequate for definitive diagnosis and by an inability to grade many malignant sarcomas. There were no significant complications resulting from the biopsies. We conclude that CNBX is a highly accurate, easily performed method for the diagnosis of large soft tissue masses that can be accomplished with minimal morbidity.

Adolescent↗

Induction of macrophage TNF alpha, IL-1, IL-6, and PGE2 production by DTH-initiating factors.

The elicitation of delayed-type hypersensitivity (DTH) reactions in mice is due to the sequential action of two different, antigen-specific, Thy-1+ cells. We have previously cloned the early-acting DTH-initiating cell from nude mice that were immunized and boosted by contact sensitization with oxazolone (OX). This cell clone, WP-3.27, releases an antigen-specific factor (OX-F) that sensitizes mast cells such that specific antigen challenge will induce serotonin release which mediates the early phase of DTH. In normal mice contact sensitized with picryl chloride (PCl), a similar polyclonal factor (PCl-F) has a similar activity and is also known to bind to macrophages. Thus, we measured macrophage production of TNF alpha, IL-1, IL-6, and PGE2 in response to the hapten affinity-purified DTH-initiating factors OX-F and PCl-F. Both factors induced significant release of each cytokine and PGE2. The production of TNF alpha, IL-1, and IL-6 was measured by bioassays. Northern blot analysis showed rapid accumulation of cytokine mRNA (2-4 hr), while maximal production of PGE2 occurred at approximately 8 hr. These macrophage activating properties of OX-F and PCl-F were not due to contamination with LPS as determined by the low levels of LPS present in OX-F and PCl-F and by the failure of polymyxin B to inhibit factor-induced PGE2 and TNF alpha production. Also, macrophage activation was shown not to be due to the action of several lymphokines known to be produced by WP3.27. Separation of OX-F and PCl-F by preparative isoelectric focusing showed a similar pattern: there were two major peaks of PGE2-inducing activity observed for both factors (for PCl-F at pI of 2-3 and 5.0, and for OX-F at pI of 3.5-4 and 5.0), but not for a sham factor produced by WEHI-3 cells. The ability of DTH-initiating factors to rapidly induce macrophage cytokine release and PGE2 synthesis 4-6 hr later may suggest a role for these mediators during the respective early vascular and late cellular phases of inflammation in DTH.

Animals↗