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PubMed2026

Phenotyping strategies for chronic overlapping pain conditions and internalizing disorders in Veterans: Prevalence, comorbidity, and latent structure as evidence for construct validity.

Chronic overlapping pain conditions (COPCs), internalizing (INT) disorders, and opioid use disorder (OUD) are common, comorbid, and difficult to phenotype at scale. Electronic health record (EHR) studies commonly define cases using Any Code (AC; ≥1 ICD-9/10 code) and Multiple Code (MC; ≥1 inpatient or ≥2 outpatient codes) phenotyping strategies, but it is unclear whether these thresholds change only case numbers or also the clinical relationships among conditions. This cross-sectional study included approximately 950,000 Million Veteran Program participants with ≥2 visits. AC and MC phenotypes for 17 conditions spanning COPCs, INT, and OUD were compared in prevalence, case characteristics, comorbidity, and latent structure. Random-thinning analysis compared AC-MC differences to case reduction alone. Construct validity was evaluated through correspondence with expected patterns of association and latent organization. Back pain (AC=58.1%; MC=48.1%), major depressive disorder (41.5%; 36.2%), and post-traumatic stress disorder (32.6%; 29.1%) were most prevalent. MC excluded 33.5% of AC cases on average, and MC cases had greater healthcare utilization, diagnostic burden, opioid exposure, and psychiatric medication use than AC-only cases. The observed mean absolute correlation change (mean |Δr|=0.014) was smaller than in all 1000 random-thinning replicates. Both strategies supported a correlated, four-factor model consistent with "Anxious Misery," "Fear," "Diffuse Pain," and "Head Pain" (AC: CFI=0.987, RMSEA=0.015; MC: CFI=0.987, RMSEA=0.014). The MC strategy reduced prevalence and altered case composition but maintained the expected comorbidity and latent organization patterns among conditions. Findings provide evidence of phenotype construct validity and inform selection of EHR phenotyping strategies for epidemiological and genomic research. PERSPECTIVE: Commonly used EHR phenotyping strategies tested in nearly one million Veterans produce broadly similar latent organization across comorbid and prevalent chronic overlapping pain conditions, internalizing disorders, and opioid use disorder. Findings support construct validity and clarify trade-offs involving case inclusion, recorded burden, and healthcare observation in large-scale research.

Chronic overlapping pain conditions↗
PubMed2005

Oral plasmablastic lymphoma in an HIV-negative patient: a case report and review of the literature.

Plasmablastic lymphoma is an HIV-associated non-Hodgkin's lymphoma that primarily affects the oral cavity and jaws. The purpose of this report is to describe the first case of plasmablastic lymphoma occurring in an HIV-negative, nonimmunocompromised individual, and to review the histopathologic and immunohistochemical phenotype of this lymphoma. Histopathologically, our case exhibited a dense, diffuse lymphocytic infiltrate of noncohesive large lymphocytes with plasmacytoid features. Immunohistochemical analysis revealed positivity for the B-cell marker CD79a, VS38c, Epstein-Barr virus latent membrane protein (LMP), immunoglobulin G (IgG), and lambda light chain restriction. Neoplastic cells were negative for leukocyte common antigen, CD20, CD3, CD10, CD138, Bcl-2, Bcl-6, desmin, actin, EMA, S-100, HMB45, Alk-1, HHV8, IgA, IgM, and cytokeratin. The features of this rare disease are summarized based on a comprehensive review of the epidemiologic, clinical and immunohistochemical findings of previously reported cases.

HIV Seronegativity↗
PubMed1999

Epstein-Barr virus infection in Richter's transformation.

Chronic lymphocytic leukemia (CLL) may convert to a diffuse large cell lymphoma (Richter's syndrome) over time. In occasional cases of Richter's transformation, Epstein-Barr virus (EBV) has been identified in the lymphoma cells. To evaluate the association of EBV infection with Richter's syndrome, the biopsy specimens and clinical records of 25 patients who were seen at the Mayo Clinic between 1984-1996 were retrospectively evaluated for the presence of EBV by immunoperoxidase staining for expression of EBV latent membrane protein (LMP), as well as the expression of EBV RNA and DNA in the cells by in situ hybridization. Four of the 25 patients showed evidence of EBV in the diffuse large cell lymphoma cells-three patients with a B-cell phenotype were positive for LMP, EBV DNA, and RNA; and one patient with a T-cell phenotype had positive EBV RNA in the large cell lymphoma cells. The Richter's syndrome was treated with combination chemotherapy in 15 patients, three received radiotherapy, three were followed without further therapy after a splenectomy, two died before treatment could be started, and one patient had insufficient follow-up. One patient with evidence of EBV in large cell lymphoma cells was treated with acyclovir as initial therapy. The median survival of EBV-positive patients was three months compared with nine months for EBV-negative patients, but this difference was not statistically significant (P = 0.385). Evidence for EBV infection related to Richter's transformation was present in 16% of the patients in this study and may be associated with a poorer outcome. Primary therapy with acyclovir in one patient did not seem to be beneficial and other therapeutic modalities in patients with EBV-positive Richter's transformation need to be explored.

Adult↗
PubMed1985

Latent and active plasminogen activator in corneal ulceration.

Previous studies of alkali burns have provided evidence for an important role of the plasminogen activator (PA)/plasmin system in corneal ulceration. Current studies have utilized a sensitive, plasminogen-dependent fluorescent assay to demonstrate that PA is present mostly in a latent (trypsin- or plasmin-activatable) form (proactivator) in cultures of rabbit corneal epithelial cells or normal corneas. Cultures of ulcerating corneas demonstrate only active PA early in organ culture, whereas, latent PA levels increase later in culture. Thus, ulceration is correlated with the apparent conversion of latent to active PA. Moreover, profiles of proactivator and latent collagenase and of active PA and active collagenase in vitro, respectively, are similar, suggesting that activator and collagenase are under coordinate control. Cultures of normal epithelial cells and nonulcerating corneas contain PA molecular weight species of 72,000 and 46,000 MW, and ulcer corneas, species of 72,000, 46,000, and 35,000 MW. Double-diffusion analysis indicates that rabbit epithelial cells, fibroblasts, and ulcer corneas produce urokinase (UK)-like PA; and human cornea extracts and tears also contain PA immunoreactive with anti-UK antibodies. The existence of PA in a latent form identifies another level of regulation in the cascades that lead to stromal ulceration.

Adsorption↗
PubMed1979

[Role of changes in the hemodynamics of the pulmonary circulation in pulmonary gas exchange].

High pressure in the lung artery was maintained with the aid of i. v. serotonin administration (0.5 mg/ml) in dogs during 10 min. The simultaneous increase of the intravascular pressure in minor circulation and of the lung volume circulation was followed by an increasing blood volume in lungs, diffusion capacity of lungs, oxygen tension in the arterial blood, and satiation of the latter with oxygen. The combined action of the above two hemodynamic factors aids to opening of latent vascular areas, to a more regular distribution of perfusion over the lung areas according to the ventilation level. This mechanism seems to be one of the first compensatory responses to disturbances in the lung gas exchange.

Animals↗
PubMed2003

[Secondary lung cancers].

Lung is the most common site of metastatic involvement for many malignant tumors. The most frequent abnormalities are solitary or multiple pulmonary nodules (large "cannonball" nodules or diffuse miliary pattern), and lymphangitic carcinomatosis. Pulmonary metastases usually occur in a context of a previously known tumour, but sometimes may reveal a latent tumour. Most patients receive palliative treatment with chemotherapy, or hormone therapy (for metastases of breast cancer, thyroid, endometrial carcinoma or prostatic cancer). Patients may rarely benefit from resection of pulmonary metastases.

Humans↗
PubMed1991

[Use of ultrasonography in prophylactic examinations at an industrial enterprise].

The authors analyze the sonography data on the abdominal organs and thyroid in 1092 blue-collar and white-collar workers of one of the Moscow enterprises. The studies were carried out using the up-to-date outfits manufactured in Japan, working in the real time mode. Deviations from normal were revealed in 285 persons (26.1%). Of these, 66.4% manifested pathological alterations in one of the organs whereas in 1/3, the alterations went together. The most frequently occurring alterations in the liver included cholecystitis (46.9%), dystrophy (31.5%) as well as diffuse alterations in the organ structure of obscure genesis (15.4%). The most frequently demonstrated alterations in the urinary system were concrements (29.5%), cysts (22.7%) as well as deformities and dilatations of the pelvi-calyceal system (31.9%). The resolving power of ultrasonography in revealing concrements in the gallbladder constituted 0.5 cm, that in the kidneys, 0.3-0.5 cm. The rate of demonstration of different alterations in the thyroid amounted to 7.5%. Among them, more than half (54.3%) were diffuse enlargements and then there followed uninodular and combined goiters. The data obtained attest to a high clinical efficacy of ultrasonography in revealing latent pathology and different deviations from normal in the abdominal organs and thyroid in the working persons. It is suggested that the given method may be widely used as the basic one in prophylactic examinations of blue-collar and white-collar workers of industrial enterprises as well as a means of objective control over the health status of the follow-up and risk groups requiring examinations made over time and special additional examinations.

Abdomen↗
PubMed1990

[Two cases of rectal carcinoma that developed as a late complication of pelvic radiotherapy].

Two cases of a pelvic evisceration have been performed, due to an irradiation-induced rectal cancer. Described are the cases of two women who had been treated with irradiation for a cervical cancer following a hysterectomy, one patient being 65 years old and the other 67. After a latent period that lasted for 12 and 24 years, respectively, each had developed a rectal cancer. In each case, case excised specimen showed diffuse fibrosis and a hyaline change, reflecting the effect of radiation on the tumoral tissue. Cases of an irradiation-induced rectal cancer are uncommon, and the symptoms of enterocolitis caused by irradiation are similar to those of a colorectal cancer. The authors therefore suggest careful and long-term follow-up of patients that have received pelvic radiation.

Adenocarcinoma↗
PubMed1985

Thorium dioxide-related angiosarcoma of the liver. Pathomorphologic study of 29 autopsy cases.

We describe the pathomorphologic features of 29 autopsy cases of thorium dioxide-related angiosarcoma (AGS) of the liver. The average (+/- SD) latent period after thorium dioxide injection was 36.2 +/- 5.2 years. Macroscopically, thorium dioxide-related AGS was divided into four types as follows: diffuse micronodular, multinodular, massive, and mixed multinodular and massive. Diffuse-micronodular and multinodular types were the most common. Histologically, thorium dioxide-related hepatic AGS was characterized by two cell types (spindle-shaped cells and polyhedral cells) and two structural patterns (sinusoidal and solid). There was no case composed of a solid pattern only. Immunohistochemically, factor VIII-related antigen was found to be positive in the endothelial cells of normal blood vessels and in the hyperplastic endothelial cells of the sinusoids, but negative in the tumor cells. Extramedullary hematopoiesis was found in both the tumorous and nontumorous areas in four cases. Erythrophagocytosis by the tumor cells was found in three cases. In the nontumorous area, varying degrees of sinusoidal dilatation with frequent hyperplastic changes of the sinusoidal lining cells were observed in all cases. These sinusoidal changes were frequently contiguous to AGS foci and were considered as a precursor change. In addition to the dominant sinusoidal changes, nodular hepatocytic hyperplasia was observed in two cases.

Adult↗
PubMed1999

Accelerated conversion of human plasminogen activator inhibitor-1 to its latent form by antibody binding.

The serpin plasminogen activator inhibitor-1 (PAI-1) slowly converts to an inactive latent form by inserting a major part of its reactive center loop (RCL) into its beta-sheet A. A murine monoclonal antibody (MA-33B8), raised against the human plasminogen activator (tPA).PAI-1 complex, rapidly inactivates PAI-1. Results presented here indicate that MA-33B8 induces acceleration of the active-to-latent conversion. The antibody-induced inactivation of PAI-1 labeled with the fluorescent probe N, N'-dimethyl-N-(acetyl)-N'-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) ethylene diamine (NBD) at P9 in the RCL caused a fluorescence enhancement and shift identical to those accompanying the spontaneous conversion of the P9.NBD PAI-1 to the latent form. Like latent PAI-1, antibody-inactivated PAI-1 was protected from cleavage by elastase. The rate constants for MA-33B8 binding, measured by NBD fluorescence or inactivation, were similar (1.3-1.8 x 10(4) M-1 s-1), resulting in a 4000-fold faster inactivation at 4.2 microM antibody binding sites. The apparent antibody binding rate constant, at least 1000 times slower than one limited by diffusion, indicates that exposure of its epitope depends on an unfavorable equilibrium of PAI-1. Our observations are consistent with this idea and suggest that the equilibrium involves partial insertion of the RCL into sheet A: latent, RCL-cleaved, and tPA-complexed PAI-1, which are inactive loop-inserted forms, bound much faster than active PAI-1 to MA-33B8, whereas two loop-extracted forms of PAI-1, modified to prevent loop insertion, did not bind or bound much more weakly to the antibody.

Antibodies, Monoclonal↗
PubMed1990

[The use of immunoenzyme analysis for recording specific IgM antibodies in syphilis patients].

Specific IgM antibodies were assayed in blood sera of 230 patients with various forms of syphilis and of 561 controls. Enzyme immunoassay (EIA) sensitivity has made up 95.8 percent for primary syphilis, 93.8 percent for secondary new, 78.3 percent for secondary recurrent, 35.4 percent for early latent, 37.5 percent for late latent, and 80 percent for unknown syphilis. False-positive reactions were recorded in 5.5 percent of cases and were as a rule seen in the sera from patients with diffuse diseases of connective tissue. IgM EIA has proved highly effective in testing the sera from patients with primary seronegative syphilis and from subjects who had sexual intercourse with patients suffering from contagious forms of syphilis.

Antibodies, Bacterial↗
PubMed1995

Characteristics of follicular tumors and nonneoplastic thyroid lesions in children and adolescents exposed to radiation as a result of the Chernobyl disaster.

BACKGROUND: In addition to the previously reported increase in incidence of thyroid carcinomas in Belarussian children after the Chernobyl disaster in April, 1986, benign thyroid lesions were also found to be increased in the exposed population. METHODS: A total of 60 follicular neoplasms and benign nonneoplastic thyroid lesions arising after the Chernobyl disaster in children and adolescents of 7 to 18 years of age were studied. RESULTS: The primary diagnoses in this series were follicular carcinoma in 1 (2%) case, follicular adenoma in 9 (15%), cystic adenomatoid nodule with papillae in 18 (30%), multinodular goiter in 18 (30%), diffuse hyperplasia in 2 (3%), diffuse hyperplasia with atypia and nodularity in 5 (8%), lymphocytic thyroiditis in 6 (10%), and thyroid cyst in 1 patient (2%). Additional histologic changes in thyroid glands from these patients were similar to those reported after radiation exposure, and included perifollicular fibrosis (72%), focal epithelial hyperplasia (73%), colloid accumulation (47%), follicular atrophy (33%), and cellular atypia (25%). Vascular abnormalities were found more often (75%) than previously reported in the thyroid gland after irradiation, and had a somewhat different appearance. They affected primarily medium-size arteries and were characterized by damage of the internal elastic lamina in addition to intimal fibrosis. CONCLUSIONS: The first case of thyroid follicular carcinoma in the exposed Belarussian children was diagnosed after a latent period of 6.5 years, as compared with 4 years of minimal latency for post-Chernobyl papillary carcinomas. Among benign thyroid lesions, cystic adenomatoid nodules of papillary type and diffuse hyperplasia with cellular atypia and nodularity seem to be commonly associated with radiation exposure to the thyroid gland.

Adenocarcinoma, Follicular↗
PubMed1990

Prostatic stromal cells and testicular peritubular cells produce similar paracrine mediators of androgen action.

The role of mesenchymal-epithelial interactions in androgen action was explored using Sertoli cells as the epithelial cells and testicular peritubular cells or prostatic stromal cells as mesenchymal cells. Footsole fibroblasts served as a control. The secretion of transferrin was used as an androgen-regulated parameter of Sertoli cell function. It is demonstrated that coculture of peritubular or stromal cells with Sertoli cells markedly increases the production of transferrin. This effect requires a 4-day latent period and is maximal with low concentrations (10%) of mesenchymal cells. Stimulatory effects of androgens can only be demonstrated at suboptimal concentrations of the latter cells. Fibroblasts are inactive. At least two mechanisms contribute to these stimulatory effects. Peritubular cells and stromal cells share the ability to promote the deposition of an extracellular matrix when cocultured with Sertoli cells. When Sertoli cells are seeded on this matrix, the production of transferrin is increased. This effect requires no latent period and is independent of the presence of androgens during the period of matrix deposition. In addition, peritubular cells and stromal cells produce diffusible mediators which increase transferrin production by Sertoli cells. In both cell types, the production of these mediators is controlled by androgens, and their action is preceded by a 4-day latency period. The mediators have a comparable mol wt (45,000) and resemble P Mod-S, known to be secreted by peritubular cells. These data suggest that mesenchymal-epithelial interactions play a role in androgen-supported maintenance of adult function and that mesenchymal tissue from different androgen target tissues produces similar or identical mediators of androgen action.

Androgens↗
PubMed2005

[Malignant lymphoma manifested by fever of unexplained origin and pure red cell aplasia in an elderly patient].

A 76-year-old woman was admitted to the University of Tokyo Hospital in June 2002 because of fever of unexplained origin. She had suffered a high grade fever (above 39 degrees C) for 2 weeks. Initial evaluation revealed elevated CRP and pancytopenia. Bone marrow aspiration (BMA) was performed, and a diagnosis of pure red cell aplasia (PRCA) was made. One month later, she complained right hypochondrial pain, and aspiration from her enlarged gall bladder was performed. Her fever and PRCA ameliorated, and she was discharged in August, 2002. In April 2003, she was readmitted to our hospital because of the recurrence of high grade fever, elevation of CRP, and pancytopenia. BMA was performed and revealed diffuse large B cell lymphoma. In the case of extranodal lymphoma which only presents pyrexia, differentiation with other diseases is very difficult especially in the elderly. It is necessary to bear in mind the possibility that a hematological malignancy, especially malignant lymphoma, can be latent in elderly patient with fever of unknown origin.

Aged↗
PubMed1998

Productive infection of Epstein-Barr virus (EBV) in EBV-genome-positive epithelial cell lines (GT38 and GT39) derived from gastric tissues.

We characterized the expression of Epstein-Barr virus (EBV) on two epithelial cell lines, GT38 and GT39, derived from human gastric tissues. The EBV nuclear antigen (EBNA) was detected in all cells of both cell lines. The EBV immediate-early BZLF 1 protein (ZEBRA), the early antigen diffuse component (EA-D), and one of the EBV envelope proteins (gp350/220) were expressed spontaneously in small proportions in the cells. EBNA 1, EBNA2, latent membrane protein 1, ZEBRA, and EA-D molecules were then observed by Western blotting in the cells. The lytic cycle was enhanced with treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or n-butyrate. The virus particles were observed in the TPA treated GT38 cells by electron microscopy. Infectious EBV was detected with the transformation of cord blood lymphocytes and also with the induction of early antigen to Raji cells by the supernatants of both cells lines. A major single and minor multiple fused terminal fragments and a ladder of smaller fragments of the EBV genome were detected with a Xhol probe in both cell lines. These epithelial cells lines and viruses will be useful in studying their association with EBV in gastric epithelial cells.

Animals↗
PubMed2002

American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning.

EPIDEMIOLOGY: Almost all cases of acute methanol toxicity result from ingestion, though rarely cases of poisoning have followed inhalation or dermal absorption. The absorption of methanol following oral administration is rapid and peak methanol concentrations occur within 30-60minutes. MECHANISMS OF TOXICITY: Methanol has a relatively low toxicity and metabolism is responsible for the transformation of methanol to its toxic metabolites. Methanol is oxidized by alcohol dehydrogenase to formaldehyde. The oxidation of formaldehyde to formic acid is facilitated by formaldehyde dehydrogenase. Formic acid is converted by 10-formyl tetrahydrofolate synthetase to carbon dioxide and water. In cases of methanol poisoning, formic acid accumulates and there is a direct correlation between the formic acid concentration and increased morbidity and mortality. The acidosis observed in methanol poisoning appears to be caused directly or indirectly by formic acid production. Formic acid has also been shown to inhibit cytochrome oxidase and is the prime cause of ocular toxicity, though acidosis can increase toxicity further by enabling greater diffusion of formic acid into cells. FEATURES: Methanol poisoning typically induces nausea, vomiting, abdominal pain, and mild central nervous system depression. There is then a latent period lasting approximately 12-24 hours, depending, in part, on the methanol dose ingested, following which an uncompensated metabolic acidosis develops and visualfunction becomes impaired, ranging from blurred vision and altered visual fields to complete blindness. MANAGEMENT: For the patient presenting with ophthalmologic abnormalities or significant acidosis, the acidosis should be corrected with intravenous sodium bicarbonate, the further generation of toxic metabolite should be blocked by the administration of fomepizole or ethanol and formic acid metabolism should be enhanced by the administration of intravenous folinic acid. Hemodialysis may also be required to correct severe metabolic abnormalities and to enhance methanol and formate elimination. For the methanol poisoned patient without evidence of clinical toxicity, the first priority is to inhibit methanol metabolism with intravenous ethanol orfomepizole. Although there are no clinical outcome data confirming the superiority of either of these antidotes over the other, there are significant disadvantages associated with ethanol. These include complex dosing, difficulties with maintaining therapeutic concentrations, the need for more comprehensive clinical and laboratory monitoring, and more adverse effects. Thus fomepizole is very attractive, however, it has a relatively high acquisition cost. CONCLUSION: The management of methanol poisoning includes standard supportive care, the correction of metabolic acidosis, the administration of folinic acid, the provision of an antidote to inhibit the metabolism of methanol to formate, and selective hemodialysis to correct severe metabolic abnormalities and to enhance methanol and formate elimination. Although both ethanol and fomepizole are effective, fomepizole is the preferred antidote for methanol poisoning.

Ethanol↗
PubMed1997

Epstein-Barr virus infection and malignant lymphomas in liver transplant recipients.

Post-transplant lymphoproliferative disease (PTLD) is a major cause of death and disease in transplant patients. We describe 4 cases with histologically confirmed malignant lymphoma arising in the Birmingham liver transplant programme between 1982 and 1995. One was an EBV-positive diffuse large B-cell lymphoma, 2 were EBV-positive Burkitt's lymphomas and the 4th was an EBV-negative Burkitt's lymphoma. Immunohistochemistry revealed expression of the EBV-encoded latent membrane protein LMP1 and of the BZLF1 trans-activator protein in 2 cases each, whereas the virus-encoded nuclear antigen EBNA2 was not detectable. All available post-transplant biopsies from the 3 patients with EBV-associated lymphoma were then studied to test whether the detection of EBV-positive cells in liver allograft biopsies could be used to identify patients at risk for the development of PTLD. Two patients showed infrequent EBV-positive cells in liver allograft biopsies up to 14 months before the occurrence of lymphoma and a marked increase in the number of such cells at the time of lymphoma diagnosis. Multiple biopsies from the 3rd patient did not reveal any EBV-carrying cells in the entire post-transplant period. Our results demonstrate a low incidence of PTLD in the Birmingham liver transplant programme. The PTLDs were morphologically high-grade malignant lymphomas. Only 3 cases were associated with EBV infection, and these showed heterogeneous patterns of EBV latent protein expression. Our results also suggest that the examination of liver allograft biopsies using EBER in situ hybridisation is not an appropriate method for identifying patients at risk of developing PTLD.

Adult↗