Clonal composition and persistence of antigen-specific circulating T follicular helper cells

T follicular helper (T_FH) cells play an essential role in promoting B cell responses and antibody affinity maturation in germinal centers (GC). A subset of memory CD4⁺ T cells expressing the chemokine receptor CXCR5 has been described in human blood as phenotypically and clonally related to GC T_FH cells. However, the antigen specificity and relationship of these circulating T_FH (cT_FH) cells with other memory CD4⁺ T cells remain poorly defined. Combining antigenic stimulation and T cell receptor (TCR) Vβ sequencing, we found T cells specific to tetanus toxoid (TT), influenza vaccine (Flu), or Candida albicans (C.alb) in both cT_FH and non-cT_FH subsets, although with different frequencies and effector functions. Interestingly, cT_FH and non-cT_FH cells specific for C.alb or TT had a largely overlapping TCR Vβ repertoire while the repertoire of Flu-specific cT_FH and non-cT_FH cells was distinct. Furthermore, Flu-specific but not C.alb-specific PD-1⁺ cT_FH cells had a “GC T_FH-like” phenotype, with overexpression of IL21, CXCL13, and BCL6. Longitudinal analysis of serial blood donations showed that Flu-specific cT_FH and non-cT_FH cells persisted as stable repertoires for years. Collectively, our study provides insights on the relationship of cT_FH with non-cT_FH cells and on the heterogeneity and persistence of antigen-specific human cT_FH cells.     

Percutaneous transluminal renal angioplasty in patients with solitary kidney

We report our experience with percutaneous transluminal angioplasty of renal arteries (PTRA) in solitary kidney patients. Our series includes 31 patients (mean age: 52 years). 7 with solitary kidney following surgical nephrectomy and 24 with functioning solitary kidney. PTR indicated in presence of stenoses ranging from 60–95 % of vessel lumen. Procedure, with 29 patients were technically successful and mean values for stenosis dropped from 77 % to 33 %. In order to assess the results technically, changes in arterial blood pressure (according to Martin's classification) and creatinine levels were considered. Of 25 followed-up patients, 13 were cured (52%), 8 improved (32%),and 4 were unchanged (16%%). Complications were observed during procedures in five patients (16. 1 % ), superimposing that of nonsolitary kidney patients. Good revasculariiation, reduction of blood pressure, preservation or even improvement of renal function and low complications, make PTRA the best procedure with solitary kidney patients.     

Preimplantation retrograde pneumoplegia in clinical lung transplantation.

OBJECTIVE: Retrograde pneumoplegia seems to improve early graft function in experimental and clinical lung transplantation. We evaluated the role of retrograde flushing in addition to antegrade pneumoplegia in clinical lung transplantation. METHODS: Fourteen patients undergoing lung transplantation were randomized into 2 groups: in group I we performed antegrade pulmonary artery flushing with alprostadil (prostaglandin E1) and modified Euro-Collins solution at the time of retrieval. In group II additional retrograde flushing through the pulmonary veins was performed at the back table, before reimplantation. Hemodynamic variables, mean airway pressure, and blood gas analysis were monitored at different time points. Postoperative volumetric monitoring was performed to assess extravascular lung water. The reimplantation response was assessed by a radiographic score; extubation time and intensive care unit stay were recorded. RESULTS: During retrograde flushing, blood and clots coming out from the pulmonary artery were observed; 2 lungs harvested from a donor with multiple bone fractures had fat emboli in the retrograde perfusate. Hemodynamic monitoring did not demonstrate any difference between the 2 groups. The ratio of arterial oxygen tension to inspired oxygen fraction, extravascular lung water, duration of intubation, and length of stay in the intensive care unit were improved in group II, but the differences did not reach statistical significance. Intrapulmonary shunt fraction was significantly improved in group II at each time point ( P =.02), as well as indexed alveolar-arterial oxygen tension gradient (P =.04), mean airway pressure (P =.04), and chest x-ray score ( P =.03). CONCLUSIONS: Preimplantation retrograde flushing is not detrimental and helps to improve early graft function.     

Hemodynamic changes during continuous infusion with dobutamine in candidates for lung transplantation. Lung Transplantation Group

BACKGROUND: The aim of this study is to analyze the effects of dobutamine (DBT) on pulmonary and systemic hemodynamics and oxygenation in lung transplant candidates. METHODS: Forty-five patients (21M, 24F) to be introduced in waiting list for lung transplantation were studied (14 pulmonary fibrosis, 15 COPD, and 16 cystic fibrosis). They were studied awake, while spontaneously breathing in two different phases: baseline--O2 100%; DBT phase--O2 100% after 10 minutes of DBT continuous infusion (10 mcg/Kg/min). Blood gas samples and hemodynamic data were collected during right heart catheterization. Data were statistically analyzed with Student's "t" test and values for p < 0.05 were considered as significant. RESULTS: During DBT phase, a significant increase of cardiac output with a decreasing in systemic and pulmonary vascular resistance was observed. Since the fall in pulmonary vascular resistance (PVRI) was not proportional to the increase of cardiac output, mean pulmonary artery pressure and transpulmonary gradient increased. The prevalent role of vascular recruitment as mechanism in PVRI reduction during DBT is supported by the concomitant fall in PaO2/FiO2. This strongly suggests a worsening of regional Va/Qc due to an increased perfusion of poorly ventilated areas. CONCLUSIONS: DBT reduces PVRI through a recruitment of vessels due to an increase of pulmonary flow. Dobutamine has a favorable hemodynamic effect in mild-to-moderate pulmonary hypertension in lung transplant candidates.     

A characterization of the activity of α-1,3,5-triglycidyl-s-triazinetrione,a novel antineoplastic compound

Summary To extend initial results on the antineoplastic activity of -1,3,5-triglycidyl-s-triazinetrione (TGT, NSC 296934), a novel triepoxidic derivative, this compound was tested in a series of murine transplantable tumors. Repeated daily treatments with well-tolerated systemic doses of this chemical produced substantial retardation in tumor growth and significant prolongation of survival in the line 16 mammary, M5067 ovarian, and Madison 109 lung carcinomas and in mFS6 fibrosarcoma. Very marked activity was also seen in the P815 mastocytoma, B16 melanoma, line 38 colon carcinoma, and an intracerebrally transplanted ependymoblastoma, with high proportions of cures after one or two injections in IP transplanted SL2 lymphoma and line 26 colon carcinoma. It is concluded that the high level of antineoplastic effectiveness and the wide spectrum of TGT activity together with its novel structural characteristics could be of clinical significance.     

Reduced cardiotoxicity of doxorubicin given in the form ofN-(2-hydroxypropyl) methacrylamide conjugates: an experimental study in the rat

Summary A rat model was used to evaluate the general acute toxicity and the late cardiotoxicity of 4 mg/kg doxorubicin (DOX) given either as free drug or in the form of threeN-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates. In these HPMA copolymers, DOX was covalently bound via peptide linkages that were either non-biodegradable (Gly-Gly) or degradable by lysosomal proteinases (Gly-Phe-Leu-Gly). In addition, one biodegradable conjugate containing galactosamine was used; this residue was targeted to the liver. Over the first 3 weeks after the i.v. administration of free and polymer-bound DOX, all animals showed a transient reduction in body weight. However, the maximal reduction in body weight seen in animals that received polymer-bound DOX (4 mg/kg) was significantly lower than that observed in those that received free DOX (4 mg/kg) or a mixture of the unmodified parent HPMA copolymer and free DOX (4 mg/kg;P<0.01). Throughout the study (20 weeks), deaths related to cardiotoxicity were observed only in animals that received either free DOX or the mixture of HPMA copolymer and free DOX; in these cases, histological investigations revealed marked changes in the heart that were consistent with DOX-induced cardiotoxicity. Sequential measurements of cardiac output in surviving animals that received either free DOX or the mixture of HPMA copolymer and free DOX showed a reduction of 30% in function beginning at the 4th week after drug administration. The heart rate in these animals was 12% lower than that measured in age-matched control rats (P<0.05). Animals that were given the HPMA copolymer conjugates containing DOX exhibited no significant change in cardiac output throughout the study (P<0.05). In addition, no significant histological change was observed in the hearts of animals that received DOX in the form of HPMA copolymer conjugates and were killed at the end of the study. However, these animals had shown a significant increase in heart rate beginning at 8 weeks after drug administration (P<0.01). This study demonstrates that covalent binding of DOX to HPMA copolymer conjugates via both stable and biodegradable peptidyl linkages considerably reduces both the general acute toxicity and the late cardiotoxicity of DOX in the rat and could offer the potential for improving the therapeutic index in the clinical application of DOX.     

Assessment of thyroidal "C" cell secretion in osteoporotic girls with Turner''s syndrome. Basal and calcium-stimulated levels of total calcitonin, extractable calcitonin and katakalcin

Osteoporosis is a common finding in Turner's syndrome. To test the hypothesis that calcitonin deficiency may contribute to bone mineral loss in Turner's syndrome, we studied basal and calcium-stimulated (2 mg/kg body weight in 5 min) levels of total calcitonin, extractable calcitonin and katacalcin in 15 girls with Turner's syndrome and osteoporosis. Fifteen age-matched healthy girls were studied as controls. Both basal calcitonin (total and extractable) and katacalcin values were not significantly different in patients with Turner's syndrome in comparison with those of the controls. The calcium stimulation test showed a similar "C" cell secretory reserve in both groups. The calculation of delta CT/delta iCa of total and extractable calcitonin and delta KC/delta iCa, which accounts for individual variations in serum ionized calcium increases, did not show any significant difference between girls with Turner's syndrome and controls. We conclude that calcitonin deficiency is not a causative factor of osteoporosis in girls with Turner's syndrome and that in this syndrome long-life estrogen deficiency does not impair "C" cell secretory activity.     

Ophthalmic herpes zoster with contralateral hemiparesis: a case report

Summary Neurological complications following rubella are only rarely encountered. However, in many cases severe neurological impairment may occur, leading to permanent disability. In a recent epidemic of rubella in Israel during the years 1978–1979, 20 patients with severe neurological complications have been seen. We report on 5 cases of which 3 are described in detail. Considering the efficacy of immunization against rubella, we suggest that in countries such as England and Israel in which periodic epidemics of rubella occur, a generalized plan of immunization should be undertaken during the first years of life. Such an approach will prevent the neurological complication of congenital, as well as acquired, rubella infection.

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Zusammenfassung Obwohl neurologische Komplikationen nur selten nach Rubella erscheinen, sind sie in vielen Fällen schwer und können zu permanenten neurologischen Schäden führen. In einer Rubella-Epidemie, die kürzlich in Israel auftrat (1978–1979), wurden 20 Fälle von schweren neurologischen Komplikationen festgestellt. Wir berichten über 5 dieser Fälle, 3 von ihnen in ausführlicher Weise. Nachdem Rubella-Impfung sehr wirksam ist, schlagen wir vor, daß in Ländern wie Israel oder England, in denen Epidemien von Zeit zu Zeit auftreten, ein allgemeiner Impfungsplan für die ersten Lebensjahre eingeführt wird. So ein Plan kann die neurologischen Komplikationen nach kongenitaler oder erworbener Rubella verhindern.

     

Lipoplastics of Legs: Our Experience with a New Cannula Compared with Classical Technique

The Authors compare the results obtained between two groups of patients suffering from leg lipodystrophy, who were subjected to a reducing lipoplasty. In the first group, surgeons made use of a new sort of cannula, deprived of the classical grip, whereas in the second group, they employed the traditional probe. The best results, achieved with the first group, prove this new operating system is really effective, particularly on legs, for the following reasons: (1) Higher precision and better control of the instrument (2) Swan-neck cannula abolition (3) Opportunity to operate with both hands (4) Halved operating time (5) No tiredness after the operation.