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Lymphovascular invasion (LVI) predicts poor survival in patients with pathologically localized or locally advanced upper urinary tract urothelial carcinoma (UT-UC). However, LVI is associated with high tumor grade, tumor necrosis, advanced tumor stage, tumor location, concomitant carcinoma in situ, lymph node metastasis, and sessile tumor architecture. These factors might interfere with the analysis of the impact of LVI on oncological prognosis. To address this, this study aimed to clarify the relationship between LVI and patient prognosis in UT-UC using propensity score weighting. Data were collected from 789 patients with UT-UC treated with radical nephroureterectomy without chemotherapy. We evaluated the significance of LVI in predicting metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) using propensity score weighting. All weighted baseline characteristics included in the propensity score model were balanced between the LVI (+) and LVI (-) groups. The MFS, CSS, and OS were all significantly poorer in the LVI (+) group. For patients without LVI, the 5-year MFS, CSS, and OS rates were 65.3%, 73.1%, and 67.3%, respectively, whereas the corresponding rates were 50.2%, 63.8 %, and 54.6%, respectively, for patients with LVI. (all P < .001). For patients without LVI, the 10-year MFS, CSS, and OS rates were 61.5%, 69.6%, and 59.2%, respectively, whereas those for patients with LVI were 44.5%, 57.0%, and 42.7%, respectively (all P < .001). LVI is an important pathological feature that predicts metastasis development and worse survival outcome after radical surgery in UT-UC patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: We explored the relationships between depression and pain during acute electroconvulsive therapy (ECT) and the follow-up period for patients with treatment-resistant depression and concomitant pain., Methods: During the acute ECT phase, treatment-resistant depression patients (N = 97) were randomized to receive ECT plus agomelatine 50 mg/d, or ECT plus placebo. Depression and pain severities were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17), and the pain subscale of the Depression and Somatic Symptoms Scale at baseline, after every 3 ECT treatments, and after acute ECT. If patients achieved response (ie, a ≥ 50 % reduction in HAMD-17) or received at least 6 ECT treatments, they were prescribed agomelatine 50 mg/d and participated in a 12-week follow-up trial. The HAMD-17 and pain subscale were assessed at 4-week intervals. Both HAMD-17 and pain subscale scores were converted to T score units to compare the degrees of changes between depression and pain during acute ECT and the follow-up period., Results: Eighty-two patients completing at least the first 3 ECT treatments entered the analysis. Both HAMD-17 and pain subscale decreased significantly after acute ECT. Changes of HAMD-17 T scores were significantly greater than changes of pain subscale T scores during acute ECT and follow-up period., Conclusions: Pain changed more slowly than did depression while measuring both during acute ECT and the follow-up period. Pain can, therefore, be considered a separate entity from depression., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The International Society on Thrombosis and Haemostasis (ISTH) scoring system has been used for diagnosing overt disseminated intravascular coagulation (DIC). However, the cut-off points of fibrin-related markers remain unclear. The ability of the ISTH DIC score and Multiple Organ Dysfunction (MODS) score to predict mortality in cases of exertional heat illness (EHI) was tested. In the process, 3 different D-dimer cut-off values for diagnosing overt DIC were evaluated.Data were obtained on the first day of hospitalization for 76 patients with EHI. The DIC score was calculated according to the ISTH scoring system using 3 D-dimer cut-off values.In predicting mortality, methods 1 and 2 had the same sensitivity and specificity, which were 85% and 73.2%, respectively. The sensitivity for method 3 was 70%. Furthermore, the specificity of the DIC score for method 3 was 89%, which was higher than that of the other 2 methods. The correlation coefficients of the DIC and MODS scores of these 3 methods were 0.757, 0.748, and 0.756, respectively. For the prediction of mortality, the area under the receiver operating characteristic (ROC) curve for the DIC scores of these 3 methods was 0.838, 0.842, and 0.85, respectively. Furthermore, the area under the ROC curve of the MODS score was 0.927.The DIC score had a certain predictive power of a poor outcome of EHI patients, but this was not better than the MODS score. The present data may serve as a reference in selecting the appropriate D-dimer cut-off point for the ISTH DIC score., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Whether a strategy of postoperative non-sedation produces better outcomes compared with sedation in patients after head and neck reconstruction remains controversial. Therefore, we retrospectively investigated outcomes in 150 of these patients in our institution.Patients with head and neck cancer that received free anterolateral thigh flap were studied retrospectively, and were categorized in terms of their postoperative care into "sedation" and "non-sedation" groups. The related parameters of each patient were collected for analysis.Overall, 150 patients were included (sedation protocol (N = 56) and non-sedation strategy (N = 94)). No significant differences were observed between groups in patient demographics or postoperative outcomes. Significantly shorter durations of mean and median intensive care unit (ICU) length of stay, mechanical ventilation, hospitalization, and operative time were observed in the non-sedation group than in the sedation group. Among all patients, the sedation and flap reopen were the common variables related to prolonged ICU stay, mechanical ventilator duration, and hospitalization.The current study suggested the strategy of postoperative non-sedation is associated with a significant decrease in the duration of mechanical ventilation, ICU length of stay, hospitalization. Regardless of hospital stay, there were no differences in postoperative outcome between 2 groups.

Objectives: Major depressive disorder is a recurrent illness. Treatment strategies are generally focused on achieving remission and preventing relapse/recurrence. The aim of this study was to explore the risk factors associated with relapse for remitted patients during the 12-week follow-up., Methods: This was an open-label trial for major depressive disorder patients receiving acute treatments with electroconvulsive therapy (ECT) and continuation medication in the 12-week follow-up. Symptom severity and psychosocial functioning were assessed using the 17-item Hamilton Rating Scale for Depression (HAMD-17) and the Work and Social Adjustment Scale at each visit. Remission was defined as a HAMD-17 of 7 or less after acute treatment. Relapse was defined as a HAMD-17 of 14 or greater. Subjects achieving remission after acute treatments were included for analysis. Survival analysis was used to investigate the factors associated with relapse., Results: Sixty patients receiving ECT for acute treatment were enrolled for 12-week follow-up. Using Cox regression analysis, a greater number of previous major depressive episodes and greater baseline Work and Social Adjustment Scale scores were significantly associated with shorter time to relapse., Conclusions: The goal of acute treatment should focus on functional remission to prevent relapse. Further studies related to more effective treatments to prevent relapse after acute ECT are required in the future.

During the acute phase of vomiting, even a small amount of water may not be tolerated by mouth. Early refeeding may cause re-vomiting in patients, whereas late refeeding may result in dehydration and hypoglycemia. Nil per os (NPO) may be generally recommended by primary physicians, but the appropriate NPO duration for these patients is still unclear.The study aimed to identify the ideal NPO duration for patients with acute vomiting.We prospectively recruited patients with vomiting who underwent NPO management and were administered antiemetic agents in the emergency department (ED) and the pediatric ED. The demographics, final diagnosis, clinical manifestations, medical management, NPO duration, and laboratory data were collected and analyzed to identify the ideal NPO durationA total of 304 patients with vomiting who were admitted in the ED were enrolled. The major diagnosis was acute gastroenteritis (AGE) (82.9%), followed by acute gastritis and colitis. Most patients were younger than 6 years (43.8%). Apart from abdominal pain and vomiting, nausea was the most common symptom (93.1%). NPO duration of 4 to 6 hours had the lowest rate of refeeding failure (3.7%) compared to the other NPO durations.For patients with acute vomiting who are admitted to the ED, NPO duration of 4 to 6 hours may be necessary and should be recommended by primary ED physicians.

Rationale: Lymphoma with an initial manifestation of ascites and peritoneal invasion is rare., Patient Concerns: A 65-year-old woman presented to the emergency department with a 3-week history of abdominal distention, anorexia, and night sweating, and a 2-week history of melena. She was a silent hepatitis B virus carrier. Abdominal ultrasound showed massive ascites without cirrhosis. Abdominal computed tomography revealed ascites, infiltrative peritoneal lesions with omental cake appearance, and lymphadenopathies., Diagnosis: We performed paracentesis and the ascites cytology was obtained. The patient also underwent esophagogastroduodenoscopy, which showed ulcerative tumors in the stomach. Both ascites cytology and pathology of the gastric tumors confirmed the diagnosis of B-cell lymphoma., Interventions: This patient received 7 cycles of chemotherapy., Outcomes: Follow-up imaging studies revealed partial remission of lymphoma, but an enlargement of residual tumors in omentum and mesentery, which resulted in intractable ascites and rapid deterioration of performance status. Despite a change of regimen of chemotherapy, this patient expired 10 months after diagnosis., Lessons: Lymphoma should be one of the differential diagnoses in patients with intractable ascites not attributable to other comorbidities.

Accurate body temperature (BT) measurement is critical for immediate and correct estimation of core BT; measurement of changes in BT can provide physicians the initial information for selecting appropriate diagnostic approach and may prevent unnecessary diagnostic investigation. This study aimed to assess differences in tympanic and temporal temperatures among patients with fever in different conditions, especially in those with and without chills. This prospective study included patients from the emergency department between 2011 and 2012. All temperature measurements were obtained using tympanic thermometers and infrared skin thermometers. Differences in tympanic and temporal temperatures were analyzed according to 6 age groups, 5 ambient temperature groups, and 6 tympanic and temporal temperature subgroups. General linear model analysis and receiver operating characteristic curve analysis were used to estimate the differences in mean tympanic and temporal temperatures. Of the 710 patients enrolled, 246 had tympanic temperature more than 38.0°C, including 46 with chills (18.7%). Fourteen patients (3.0%) had chills and tympanic temperature less than 38°C. In the tympanic temperature subgroup of 39.0 to less than 39.5°C, approximately one-third of the patients had chills (32.3%). In the tympanic temperature subgroup of 38.0 to less than 39.0°C, the tympanic temperature was 0.4°C higher than the temporal temperature in patients without chills and 0.9°C higher in patients with chills. In the tympanic temperature subgroup of 39.0°C or more, tympanic temperature was 0.7°C higher than temporal temperature in patients without chills and 0.8°C higher in patients with chills. Temporal thermometer is more reliable in the age group of less than 1 year and 18 to less than 65 years. When the patients show tympanic temperature range of 38.0 to less than 39.0°C, 0.4°C should be added for patients without chills and 0.9°C for patients with chills to obtain core temperature. However, in patients with tympanic temperature of 39.0°C or more, 0.7°C to 0.8°C should be added, regardless of the presence of chills.

Previous studies have shown that urinary calculi are associated with increased risks of urinary tract cancers. However, the association between urinary calculi and overall cancers is a largely undefined body of knowledge. We conducted a nationwide population-based cohort study using Taiwan's National Health Insurance Research Database from 2000 and 2009. Patients were excluded if they had antecedent cancers or urinary calculi before the enrollment. All study subjects were followed until the occurrence of cancer, dropout from the NHI program, death, or the end of 2010. Patterns of cancer incidence in patients with urinary calculi were compared with those of the general population using standardized incidence ratio (SIR). A total of 43,516 patients with urinary calculi were included. After a median follow-up of 5.3 years, 1891 patients developed cancer. The risk of overall cancers was significantly increased (SIR, 1.75; 95% confidence interval [CI], 1.68-1.83). We observed that urinary calculi was associated with higher risk of cancers of kidney (4.24; 95% CI, 3.47-5.13), bladder (3.30; 95% CI, 2.69-4.00), thyroid (2.50; 95% CI, 1.78-3.40), hematologic origin (2.41; 95% CI, 1.92-2.99), breast (1.84; 95% CI, 1.54-2.20), lung (1.82; 95% CI, 1.59-2.07), digestive tract (1.69; 95% CI, 1.57-1.82), and head and neck (1.54; 95% CI, 1.32-1.79), respectively. Our study shows that urinary calculi are associated with higher risk of systemic cancers in addition to urinary tract cancers. Further study is required to validate this association.

Background: Substantial infective endocarditis (IE)-related morbidity and mortality may occur even after successful treatment. However, no previous study has explored long-term hard end points (ie, stroke, myocardial infarction, heart failure, cardiovascular death) in addition to all-cause mortality in IE survivors., Methods and Results: A nationwide population-based cohort study was conducted among IE survivors identified with the use of the Taiwan National Health Insurance Research Database during 2000 to 2009. IE survivors were defined as those who survived after discharge from first hospitalization with a diagnosis of IE. A total of 10 116 IE survivors were identified. IE survivors were matched to control subjects without IE at a 1:1 ratio through the use of propensity scores. The primary outcomes were stroke, myocardial infarction, readmission for heart failure, and sudden cardiac death or ventricular arrhythmia. The secondary outcomes were repeat IE and all-cause mortality. Compared with the matched cohort, IE survivors had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.40-1.80), hemorrhagic stroke (aHR, 2.37; 95% CI, 1.90-2.96), myocardial infarction (aHR, 1.44; 95% CI, 1.17-1.79), readmission for heart failure (aHR, 2.24; 95% CI, 2.05-2.43), sudden death or ventricular arrhythmia (aHR, 1.69; 95% CI, 1.44-1.98), and all-cause death (aHR, 2.27; 95% CI, 2.14-2.40). Risk factors for repeat IE were older age, male sex, drug abuse, and valvular replacement after an initial episode of IE., Conclusion: Despite treatment, the risk of long-term major adverse cardiac events was substantially increased in IE survivors., (© 2014 American Heart Association, Inc.)

Background: To date, the outcomes of transplant tourism have not been reported extensively. In addition, data about the accuracy of urine cytology for the detection and the role of the BK virus (BKV) in the carcinogenesis of urothelial carcinoma (UC) after renal transplantation are lacking., Methods: Three hundred seven patients who received deceased donor kidney transplants between January 2003 and December 2009 were retrospectively studied. The clinical parameters and outcomes between the domestic and tourist groups were compared. We also investigated the risk factors and role of BKV in the carcinogenesis of de novo UC by quantitative real-time polymerase chain reaction., Results: The subjects in the tourist group were older at transplantation and had a shorter dialysis time before transplantation. There were significantly higher incidence rates of BKV viruria, Pneumocystis jiroveci pneumonia, and malignancy in the tourist group. Graft and patient survival were superior in the domestic group. A total of 43 cancers were identified, and the most common type of malignancy was UC (23 patients, 53.5%). The tourist group had a significantly higher incidence of tumors. The sensitivity and specificity of urine cytology for detecting UC were 73.9% and 94.7%, respectively. Independent predictors of UC included female sex, use of Chinese herbal medicine, and transplant tourism. Only two patients (8.7%) with UC had detectable BKV., Conclusions: Transplant tourism was a risk factor for infection and de novo malignancy. Urothelial carcinoma was the most common malignancy after kidney transplantation. Regular screening for the early detection of UC by urine cytology or periodic sonographic surveys is mandatory, especially for those at high risk.

Background: Antipsychotic medications have been increasingly and more widely prescribed despite continued uncertainty about their association with the incidence of acute myocardial infarction (AMI)., Methods and Results: We investigated the risk of AMI associated with antipsychotic treatment in 56 910 patients with schizophrenia, mood disorders, or dementia first hospitalized or visiting an emergency room for AMI in 1999 to 2009. A case-crossover design was used to compare the distributions of antipsychotic exposure for the same patient across 1 to 30 and 91 to 120 days just before the AMI event. Adjustments were made for comedications and outpatient visits. The adjusted odds ratio of AMI risk was 2.52 (95% confidence interval, 2.37-2.68) for any antipsychotics, 2.32 (95% confidence interval, 2.17-2.47) for first-generation antipsychotics, and 2.74 (95% confidence interval, 2.49-3.02) for second-generation antipsychotics. The risk significantly increased (P<0.001) with elevations in dosage and in short-term use (≤30 days). Male patients, elderly patients, and patients with dementia were at significantly increased risk (all P<0.001). Physically healthier patients with no preexisting diabetes mellitus, hypertension, or dyslipidemia were at significantly greater risk (P<0.001), largely because they had been exposed to higher doses of antipsychotics (P<0.001). A study of the selected binding of antipsychotics to 14 neurotransmitter receptors revealed only dopamine type 3 receptor antagonism to be significantly associated with AMI risk (adjusted odds ratio, 2.59; 95% confidence interval, 2.43-2.75; P<0.0001)., Conclusions: Antipsychotic use may be associated with a transient increase in risk for AMI, possibly mediated by dopamine type 3 receptor blockades. Further education on drug safety and research into the underlying biological mechanisms are needed., (© 2014 American Heart Association, Inc.)

Objective: The aim of the work is to determine whether the change between primary and repeated serum inflammatory markers measured 8-12 h later may improve diagnostic accuracy in pediatric appendicitis., Methods: The study group comprised 258 pediatric patients with clinically suspected appendicitis admitted to the pediatric emergency department from 2005 to 2007. The significant changes in serum parameters between primary and repeated examinations were selected as the discriminating variables. The receiver operating characteristic curves were used to determine the cut-off values of the changes between two examinations in predicting appendicitis., Results: Receiver operating characteristic analysis showed that the cut-off values for the change in total neutrophils (3.0%) on the first day after the onset of symptoms (day 1), the changes in C-reactive protein concentration (4.5 mg/l) and in bands (1%) on day 2, and the change in C-reactive protein concentration (15.0 mg/l) on day 3 were significant serum parameters in predicting pediatric appendicitis., Conclusion: Repeated serum laboratory tests at different time points during the progression of acute appendicitis may be helpful in predicting pediatric appendicitis in the pediatric emergency department.

Objective: Survival of arteriovenous fistulas (AVFs) in hemodialysis patients is associated with both far infrared (FIR) therapy and length polymorphisms of the heme oxygenase-1 (HO-1) promoter. In this study, we evaluated whether there is an interaction between FIR radiation and HO-1 in regulating vascular inflammation., Methods and Results: Treatment of cultured human umbilical vein endothelial cells (ECs) with FIR radiation stimulated HO-1 protein, mRNA, and promoter activity. HO-1 induction was dependent on the activation of the antioxidant responsive element/NF-E2-related factor-2 complex, and was likely a consequence of heat stress. FIR radiation also inhibited tumor necrosis factor (TNF)-alpha-mediated expression of E-selectin, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-8, and the cytokine-mediated adhesion of monocytes to ECs. The antiinflammatory action of FIR was mimicked by bilirubin, and was reversed by the HO inhibitor, tin protoporphyrin-IX, or by the selective knockdown of HO-1. Finally, the antiinflammatory effect of FIR was also observed in patients undergoing hemodialysis., Conclusions: These results demonstrate that FIR therapy exerts a potent antiinflammatory effect via the induction of HO-1. The ability of FIR therapy to inhibit inflammation may play a critical role in preserving blood flow and patency of AVFs in hemodialysis patients.

Objective: A region at chromosome 22q11.21 has been reported to potentially harbor a candidate gene for schizophrenia, ZDHHC8 (zinc finger, DHHC domain containing 8; also annotated as KIAA1292) in a number of studies. This finding has been replicated in Han Chinese, but not in other ethnicity-specific studies. For further support from within the Han Chinese ethnic group, we selected two single nucleotide polymorphisms (SNP) located at the distal 5'-end (rs1633445; intron 10 of HpaII tiny fragments locus 9C, HTF9C) and the intron 4 (rs175174) of ZDHHC8 gene to test if these were associated with schizophrenia in a study sample of Taiwan., Methods: A total of 218 schizophrenia families with at least two affected siblings participated in this study. These two SNPs were genotyped using matrix-assisted laser desorption/localization ionization time of flight (MALDI-TOF) mass spectrometry., Results: Significant associations with schizophrenia were not shown from these two SNPs. After stratifying schizophrenia according to the deficit and the nondeficit of sustained attention assessed by the Continuous Performance Test, the rs1633445 showed significant association with schizophrenia in the presence of a deficit in sustained attention (P<0.04)., Conclusion: SNP rs1633445 of the HTF9C gene may be associated with a deficit in sustained attention within schizophrenia, in a Taiwanese cohort. The deficit of sustained attention may be an endophenotype of schizophrenia, and warrants further study.

An IgG1 monoclonal antibody (mAb), designated as 15F1.5, was generated against surface determinants of a dog peripheral blood-derived PHA-induced IL-2-dependent T cell line. It reacted with 65-80% of peripheral blood mononuclear cells (PBMCs), 90-95% of polymorphonuclear cells (PMNs), 65-70% of thymocytes, 85-95% of Thy-1 positive cells and 85-95% of IL-2-dependent T lymphoid cells in flow cytometry. It was nonreactive with peripheral blood red cells and platelets. It immunoprecipitated 95 and 150 Kd proteins derived from detergent solubilized lymphocyte membranes. Indirect immunofluorescent and immunoperoxidase staining of frozen tissue sections demonstrated positive reactivity to cells in lymphoid but not nonlymphoid tissues. The 15F1.5 antibody was not directly mitogenic for PBMC's. It caused significant decrease (P < or = 0.05) in the lymphoproliferative response to T-dependent B cell mitogens, such as pokeweed mitogen (PWM) and staphage lysate (SPL), without significant effects on responses to the T cell mitogens, phytohemagglutinin (PHA), and concanavalin A (Con A). The mixed lymphocyte culture (MLC) response and both the proliferative and effector arms of the cell-mediated cytotoxicity reactions (CMC) were inhibited in a dose-dependent manner. The mAb also inhibited the auto- and allolymphoproliferative reactivity of mixed lymphocyte kidney or islet cell cultures (MLKC and MLIC), and the adhesion of T lymphoblasts and PMA-treated PMNs to endothelial cells. In vivo administration of the 15F1.5 (20 mg/day for 5 days) caused an immediate and prolonged reduction in MLC responses, associated with cell binding of the mAb to PBMC and epitope modulation during the course of treatment, as indicated by flow cytometry. These results suggest that 15F1.5 is an immunomodulating antibody reacting with canine LFA-1. Thus, this mAb would be useful in studying the role of LFA-1/ICAM-1 in graft rejection as well as other inflammatory responses. It would also allow the use of an animal model to investigate the immunoregulatory effects of in vivo administration of anti-CD11/CD18 antibodies in organ/tissue transplants.

Background and Purpose: Thrombosis is one of the main complications of nephrotic syndrome; however, cerebral infarction associated with nephrotic syndrome has been rarely reported., Summary of Report: We describe acute cerebral infarction in two young men with nephrotic syndrome. Both had a hypercoagulable state based on hemostatic studies. By retrospectively reviewing the medical records of the past 10 years at our hospital, we found an additional five cases of cerebral infarction with nephrotic syndrome. Two of the patients were found to have nephrotic syndrome during admission for stroke., Conclusions: Hypercoagulability may be the major contributing factor of cerebral infarction in patients with nephrotic syndrome.

We have advanced the hypothesis that the primary autolymphoproliferative response of dog T cells in mixed lymphocyte kidney cultures (MLKC) results from their recognition of tissue-specific (kidney-associated) antigen(s) presented in conjunction with class II MHC antigens. Lymphocyte culture-derived supernatants had been found previously to upregulate class II antigen expression on kidney cells and enhance T cell activation. In the present study we have isolated and characterized dog IFN-gamma, a class II-inducing substance that is secreted in the culture supernatant of activated T lymphocytes. Dog IFN-gamma was induced with A-23187 and PMA and purified stepwise using controlled-pore glass, Mono Q anion exchange chromatography, and Superose 6-gel filtration on FPLC. The purification resulted in two molecules of 42 Kd and 31 Kd molecular weights. An IgG1 monoclonal antibody was engendered to these molecules. With this mAb reagent, in immunochemical experiments, we have developed a sensitive ELISA and a method for purifying dog IFN-gamma by affinity chromatography. Species specificity studies indicated that purified dog IFN-gamma reacted with a polyclonal rabbit antihuman IFN-gamma, but not with a mAb to human IFN-gamma. However, the antidog IFN-gamma mAb that was generated also reacted with recombinant human IFN-gamma. In in vitro biological studies, the purified IFN-gamma (two mol. wt. species) upregulated the expression of canine class II MHC molecules on dog tubular epithelial cells and the dog kidney epithelial cell line (MDCK). The antidog IFN-gamma mAb blocked T cell proliferative response to kidney cell and, by inference, the interaction between endogenously released IFN-gamma in vitro with its cell surface receptor, thus inhibiting the induced upregulation of class II. Interestingly, although antidog IFN-gamma markedly blocked the MLKC (10 micrograms mAb/well), there was no effect on the allogeneic MLC. This observation indicates that the cytokine IFN-gamma may be a uniquely key substance amplifying the immune response of T cells to tissue-associated antigens on surrogate antigen-presenting cells that require induced upregulation of class II MHC antigen expression (MLKC), in contrast to reactions in which these antigens are already constitutively expressed on the antigen-presenting cells (mixed lymphocyte culture).

Three methods, i.e., nonspecific radioimmunoassay (RIA; Incstar), fluorescence polarization immunoassay (FPIA; TDx Abbott), and high-performance liquid chromatography (HPLC), have been used for monitoring cyclosporine blood levels in renal transplantation patients. The levels obtained from 135 samples showed a modest correlation between RIA and HPLC, FPIA and HPLC, RIA and FRIA. The mean ratios of RIA to HPLC, FPIA to HPLC, and RIA to FPIA were 2.96, 4.14, and 0.73. The significant variations in cyclosporine levels result from the cross-reaction of antibody with some cyclosporine metabolites, by which these two methods often overestimate the true blood cyclosporine level. HPLC is a more effective and reliable method for pharmacokinetic studies and blood level monitoring of cyclosporine in clinical practice.

Immunoglobulins derived from sera containing anti-antiidiotypic antibodies (Ab2) generated in renal transplant recipients after OKT3 monoclonal antibody therapy, as reported in our previous study (1), have now been proved to bind to several bands of T cell membrane lysates (TCML) in immunoblotting analyses ranging in molecular weight from 40 to 55 KD. These sera also blocked the expression of the ligand binding to WT31 in flow cytometry. WT31 is a MAb that recognizes a common determinant on the T cell receptor (TCR). Immunoglobulins from these sera suppressed the activation of normal peripheral blood T lymphocytes (PBT) induced by OKT3. All patients (7/32) who developed this Ab2 had distinct culture-proved cytomegaloviral infections. In further immunoblotting studies, alpha F1, another MAb recognizing the framework of the TCR alpha chain, more deeply inserted in the T cell membrane, also showed binding to protein bands of cytomegalovirus pellet lysates derived from virus-infected embryonic fibroblasts. In addition, alpha F1 showed positive binding to several ligands in the membrane lysate of CMV-infected, but not noninfected MRC-5 cells. An anti-CMV MAb recognizing late nuclear antigen (LAb), also strongly bound to a approximately 50 KD band of TCML and several bands (approximately 34, approximately 40, and approximately 50 KD) of H33HJAJ1 (human T leukemia) cell lysate. Furthermore, alpha F1 immunoprecipitated a approximately 96 KD ligand of CMV-infected MRC5 lysate that had the same electrophoretic mobility as one of the proteins precipitable with LAb. Both LAb and alpha F1 also showed positive binding to paraformaldehyde-fixed and Triton X-100-permeabilized PBT in flow cytometry. Sera containing Ab2 blocked alpha F1 binding to acetone-fixed cytofuged PBT preparations on slides. Moreover, both alpha F1 and LAb inhibited mitogen-stimulated lymphocyte activation in vitro. These data support the notion that T cell functional abnormalities associated with CMV infection observed after treatment of transplant recipients with anti-T cell monoclonals might be caused by binding to T cell ligands by a variety of crossreacting human Igs operative in a regulatory network. Confirmatory evidence is the effect of MAbs generated against CMV virion epitopes crossreacting with T cell ligands, and vice versa.

Four of 21 renal transplant recipients treated with OKT3 for rejection episodes developed a second sustained (approximately 2 weeks) depression in CD3 peripheral blood lymphocyte cell-surface-marker expression. This occurred after OKT3 therapy had ceased, subsequent to a return toward baseline CD3 levels seen before OKT3 therapy was instituted. The second decrease in CD3 T cell counts was dissociated from CD2 marker T cell counts using flow cytometry and coincided with transient cytomegaloviral infections. Three phases of immunosuppression were defined in these 4 patients: phase I (during OKT3 treatment); phase II (after treatment when CD3 counts were reconstituted); and phase III (when CD3 counts again were depressed). During phase III, serum of the 4 affected patients could transfer a blocking effect on the expression of the CD3 marker of peripheral blood T cells of "normal" laboratory volunteers. Contained in these sera were human IgG antibodies that bound on Western blot analysis and by radioautography after immunoprecipitation to a protein band of a T cell membrane lysate with an m.w. of 23 kD. The reaction was identical to that seen with OKT3 (immunoprecipitation). Moreover, this Western blot binding could be virtually (but not completely) eliminated by multiple absorptions of the T cell membrane lysate with OKT3. By using an affinity-purified human anti-OKT3 IgG from one of the 4 patients, it was possible to immunoabsorb from phase III sera the CD3 blocking activity as well as the binding to the 23 KD protein band. A reverse immune absorption by the phase III sera with the anti-OKT3 IgG after ultracentrifugation prevented the anti-OKT3 IgG from binding to OKT3 coated plates in solid-phase radioimmunoassay. These data support the notion that autoimmune human anti-anti-id (Ab2) antibodies can occasionally be generated by treatment with OKT3, which are directed against CD3 complex epitopes similar to the ligand of OKT3.

A 72 year old woman complained of transient loss of vision in the left eye. She had undergone a left carotid endarterectomy 10 years previously. Reduced ophthalmic artery pressure was found on noninvasive carotid artery testing and cerebral angiography was performed. No lesion was evident in the carotid artery, but significant ophthalmic artery stenosis was identified. We report this case as showing the occurrence of amaurosis fugax in association with ophthalmic artery stenosis.

A 45-year-old man awoke with numbness and paresthesias on the right side of his face, scalp, ear, and tongue. CT and MRI demonstrated a focal hemorrhage in the dorsolateral right pontine tegmentum. Cerebral angiography was negative for vascular malformation or aneurysm. CT performed 1 month later showed complete resolution of the pontine hematoma, with residual minimal lateral pontine atrophy.