Production of immune interferon is regulated by more than one T cell subset: Lyt-1,2,3 and Qat-5 phenotypes of murine T lymphocytes involved in IFN-γ production in primary and secondary mixed lymphocyte reaction

Lymphocytes responsible for the production of IFN-γ (immune interferon) in primary and secondary mixed lymphocyte reactions have been characterized with antisera specific for the Lyt-1,2,3 and Qat-5 alloantigens. A comparison was made between selected T cell subsets with respect to their ability to proliferate, generate cytolytic activity and produce IFN-γ in response to H-2 alloantigens. The data indicate that (a) in primary mixed lymphocyte reactions, IFN-γ is produced by Lyt-1⁺, Qat-5⁺ and by Lyt-123⁺, Qat-5⁺ T cells, (b) in secondary mixed lymphocyte reactions, an additional T cell subset, which is Lyt-23⁺, Qat-5^?, participates in the generation of IFN-γ and (c) the production of IFN-γ does not correlate with either proliferation or the generation of cytotoxic lymphocytes.     

The anticytomegaloviral activity of raltitrexed is abrogated in quiescent mouse fibroblasts that overexpress thymidylate synthase

Cytomegalovirus (CMV) replication in non-proliferating cells requires the coordinated expression of the host enzymes responsible for deoxyribonucleotide synthesis. Thymidylate synthase (TS) is an essential cellular enzyme that catalyzes de novo synthesis of thymidylic acid (dTMP). In this report we show that murine CMV (MCMV) replication and DNA synthesis are inhibited in quiescent 3T6 fibroblasts by raltitrexed, a quinazoline-based folate analog that specifically inhibits TS. This antiviral activity was abrogated in LU3-7 cells, a 3T6 derivative that overproduces TS by about 50-fold. These observations indicate that the anticytomegaloviral activity of raltitrexed is associated with TS inhibition and suggest that cellular TS activity is required for efficient CMV replication in quiescent cells.     

Effects of ACE inhibition in normotensive patients with chronic glomerular disease and normal renal function

A double-blind, placebo-controlled study was carried out to assess the effects of a three-month treatment with a new ACE inhibitor, Benazepril (BNZ), on systemic and renal hemodynamics, and urine protein excretion, in 20 patients with chronic glomerulonephritis, normal blood pressure (130/83 +/- 16/10 mm Hg), and normal renal function (creatine clearance 106 +/- 25 ml/min). Treatments with placebo or BNZ were assigned randomly. A wide range of proteinuria lowering effect was observed in overall population (from 1 to 84%, average 34%). Following the arbitrary level of a 30% reduction, two well-matched subgroups (10 patients for each one) were obtained: "good responders" (average decrease 51%), and "poor responders" (average decrease 17%). The main distinctive feature between the two groups was a higher plasma renin activity level in good than in poor responders. A positive correlation between the fall in proteinuria and blood pressure was found. Although the decrease in blood pressure seems to represent the major factor in determining the reduction in proteinuria, a multiple correlation analysis showed that the most prominent role (71%) was attributable to the combined decrease in blood pressure and filtration fraction, and then also to the efferent arteriole dilatation. Our conclusion is that ACE inhibitors are capable of also reducing proteinuria in patients with renal disease with normal blood pressure, the effect being more pronounced in those exhibiting humoral, systemic and renal hemodynamic patterns, indicating a greater activity of circulating and renal renin angiotensin system.     

SHAFT syndrome revisited

Wallace aptly described patients with overriding psychological problems and upper extremity complaints as possessing the Shaft syndrome. SHAFT patients studied fell into two categories. The first group inflicted physical harm on themselves, creating factitious injuries. The second group postured their limbs in attitudes that are not explainable anatomically. This latter group is described by Simmons as the clenched fist syndrome. Although patients who had factitious injuries invariably healed with protective casting, 4 patients relapsed. Eight of 14 patients who were employed at the onset of their complaints returned to gainful employment. Some patients received psychological counseling but most lacked sufficient insight to make gainful progress. Reaching a diagnoses was often difficult. At least 5 patients had unwarranted operations. The surgeon needs a high index of suspicion when the history and findings do not match for patients harboring complaints of pain, numbness, stiffness, or inability to use their limb.     

Berengario da Carpi

Berengario da Carpi was magister of anatomy and surgery at the University of Bologna from 1502 to 1527. Eustachio and Falloppia defined him as 'the restaurator of anatomy'. He was a great surgeon, anatomist and physician of illustrious patients including Lorenzo II dei Medici, Giovanni dalle Bande Nere, Galeazzo Pallavicini, Cardinal Colonna, and Alessandro Soderini. He had strong links to the intellectuals of his time (Forni, Bonamici, Manuzio, Pomponazzi) as well as with the Medici family. He was respected by the Popes Julius II, Leo X and Clement VII. His main contributions are the Isogogae Breves, De Fractura calvae sive cranei, and the illustrated Commentaria on the Anatomy of Mondino de Liucci, a textbook utilized for more than 200 years, which Berengario aimed to restore to its initial text. The Commentaria constitutes the material for the last part of this paper which concludes with a personal translation of some passages on 'The kidney', where the author gives poignant examples of experimental ingenuity.     

Osijek Health Center during the 1991-1992 war in Croatia

To assess the effectiveness of health services in the city of Osijek during the 1991-1992 war in Croatia, we followed the changes in the utilization of health services, morbidity and mortality, and completion of a vaccination plan during the 2 years of the war. We used a retrospective analysis of data from the Osijek Health Center and the Osijek County Institute of Public Health. The organization of health care during the war followed the concept of integrated health care and the instructions of the Ministry of Health. Visits to primary health care physicians decreased considerably, with a concomitant increase in disease and mortality. The plan for mandatory vaccination was not completed because of the evacuation of preschool and school children. The war changed the mode of health care use, the disease and mortality structure, and the implementation of mandatory vaccination. However, timely education and preparation of the health services to the war situation resulted in an adequate provision of health care to the population.     

Preliminary report on the association of apolipoprotein E polymorphisms, with postoperative peak serum creatinine concentrations in cardiac surgical patients

BACKGROUND: Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated with major increases in morbidity, mortality, and cost. Genetic polymorphisms have been implicated as a factor in the progression of chronic renal disease, but a genetic basis for the development of acute renal impairment has not been investigated. The authors therefore tested the hypothesis that apolipoprotein E alleles are associated with different postoperative changes in serum creatinine after cardiac surgery. METHODS: The authors performed a prospective observational study with use of data from 564 coronary bypass surgical patients who were enrolled in an ongoing investigation of apolipoprotein E genotypes and organ dysfunction at a university hospital between 1989-1999. Renal function was assessed among apolipoprotein E genotype groups by comparisons of preoperative (CrPre), peak in-hospital postoperative (CrMax) and perioperative change (DCr) in serum creatinine values. RESULTS: The epsilon4 allele grouping (E2 = 2/2,2/3,2/4; E3 = 3/3; E4 = 3/4,4/4) was associated with a smaller increase in postoperative serum creatinine (perioperative change: E4, +0.17; E3, +0.26; E4, +0.27 mg/dl) and a lower peak postoperative creatinine than the epsilon2 and epsilon3 in univariate and multivariate analysis (peak in-hospital postoperative serum creatinine multivariate P = 0.015 vs. epsilon3, P = 0.038 vs. epsilon2). There was no difference in baseline creatinine among allele groups. CONCLUSIONS: Inheritance of the apolipoprotein epsilon4 allele is associated with reduced postoperative increase in serum creatinine after cardiac surgery, compared with the epsilon3 or epsilon2 allele. This is the first report of a possible genetic basis for acute renal impairment. These data may contribute to renal risk stratification for cardiac surgery and raise questions regarding apolipoprotein E and the pathophysiology of acute renal injury.     

Impaired Vagal Activity in Long-COVID-19 Patients

Long-COVID-19 refers to the signs and symptoms that continue or develop after the “acute COVID-19” phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized β-coefficient = 0.259), NT-ProBNP (standardized β-coefficient = 0.281), HF component of spectral analysis (standardized β-coefficient = 0.696), and LF/HF ratio (standardized β-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.