3q−, 3q+ anomaly in malignant proliferations in humans

Anomalies of both No. 3 chromosomes, of the t(3q?; 3q+) type can be observed in human malignancy as reported previously. It is our experience that this anomaly is found predominantly in myeloproliferative disorders, as a rather rare event, though occurring more frequently than similar exchanges between other homologous chromosomes. Previous claims about a relationship between this anomaly and thrombocytosis could not be confirmed, but the features found in a few patients indicate that further research should be undertaken to clarify this point.     

Effects of saline loading on jejunal absorption of calcium,sodium, and water,and on parathyroid hormone secretion in the rat

Summary To investigate whether intestinal calcium absorption parallels that of sodium following extracellular fluid volume expansion, the effects of saline loading on intestinal transport of calcium. sodium and water were studied in rats by perfusing jejunal loops in situ.After calcium-free saline infusion net calcium absorption was reversed similar to that of sodium and water and net secretion occurred. Concurrently, blood-to-lumen (b-l) calcium flux, measured using⁴⁵Ca, increased significantly (P<0.001). Following expansion with calcium-containing Ringer a similar reversal of net calcium, sodium and water flux was also observed. Again, the b-l calcium flux increased but to a significantly lesser extent (P<0.05). Plasma ionized calcium remained unchanged after calcium-rich Ringer loading, but decreased significantly (P<0.001) when calcium was omitted from the solution. Plasma immunoreactive parathyroid hormone was unchanged after expansion with the calcium containing solution but increased following calcium-free infusion.It is concluded that after extracellular fluid volume expansion: 1. net jejunal calcium absorption is decreased; 2. the decrease parallels that of sodium and water; 3. b-l calcium transport is enhanced to a greater degree by calcium-free Ringer infusion than by a calcium-rich solution. This difference could be the result of increased parathyroid hormone secretion.     

Ligand-induced autoregulation of IL-2 receptor {alpha} chain expression in murine T cell lines

The IL-2 receptor (IL-2R) is composed of three chains a, ßand . In mice, contrary to the human system, we have previouslydemonstrated that the IL-2Rß complex does not bindIL-2. Therefore, mouse IL-2 response is completely dependenton the expression of the IL-2R gene product. T cell clones expressingmouse IL-2Rß and the human IL-2R transgene have beenstudied. When cells are grown in IL-4, mouse IL-2R is not expressed.However, exposure to IL-2 leads to the expression of the endogenousmurine IL-2R subunit. The T cell line expressing mouse IL-2Rand human IL-2Rß can grow in IL-2 but does not expressendogenous murine IL-2 R. Transfection of these cells with thehuman IL-2R gene restores the capacity to induce murine IL-2R.This result demonstrates that IL-2-IL-2R interactions are requiredfor induction of IL-2R. The kinetics of induction and deinductionof murine IL-2R have been studied using clone 18.III. From negativecells, expression of murine IL-2R is a very slow phenomenon.From cells fully expressing IL-2R, deinduction is a two-stepprocess: after a rapid decrease of IL-2R the cells continueto express, for a long period of time, basal levels of murineIL-2R. When cells expressing basal levels of IL-2R are exposedto IL-2, induction of IL-2R is a very rapid phenomenon. Theautoregulatory loop formed by IL-2-IL-2R therefore displaysdifferent levels of functioning.     

Vaccine-induced binding and neutralizing antibodies against Omicron 6 months after a homologous BNT162b2 booster

Evidence about the long-term persistence of the booster-mediated immunity against Omicron is mandatory for pandemic management and deployment of vaccination strategies. A total of 155 healthcare professionals (104 COVID-19 naive and 51 with a history of SARS-CoV-2 infection) received a homologous BNT162b2 booster. Binding antibodies against the spike protein and neutralizing antibodies against Omicron were measured at several time points before and up to 6 months after the booster. Geometric mean titers of measured antibodies were correlated to vaccine efficacy (VE) against symptomatic disease. Compared to the highest response, a significant 10.2- and 11.5-fold decrease in neutralizing titers was observed after 6 months in participants with and without history of SARS-CoV-2 infection. A corresponding 2.5- and 2.9-fold decrease in binding antibodies was observed. The estimated T_1/2 of neutralizing antibodies in participants with and without history of SARS-CoV-2 infection was 42 (95% confidence interval [CI]: 25–137) and 36 days (95% CI: 25–65). Estimated T_1/2 were longer for binding antibodies: 168 (95% CI: 116–303) and 139 days (95% CI: 113–180), respectively. Both binding and neutralizing antibodies were strongly correlated to VE (r = 0.83 and 0.89). However, binding and neutralizing antibodies were modestly correlated, and a high proportion of subjects (36.7%) with high binding antibody titers (i.e., >8434 BAU/ml) did not have neutralizing activity. A considerable decay of the humoral response was observed 6 months after the booster, and was strongly correlated with VE. Our study also shows that commercial assays available in clinical laboratories might require adaptation to better predict neutralization in the Omicron era.     

Testicular degeneration in three patients with the persistent müllerian duct syndrome

The presistent Müllerian duct syndrome, characterized by the presence of uterus and tubes in males, is a familial disorder due to defects of synthesis or action of anti-Müllerian hormone, a Sertoli cell glycoprotein responsible for the regression of Müllerian derivatives in normal male fetuses. Patients are normally virilized and testicular production of testosterone is normal. Both testes my be cryptorchild; alternatively, one may be descended into the inguinal canal or scrotum, together with the Müllerian derivatives, a condition known as hernia uteri inguinalis. We have recently observed three patients affected by the presistent Müllerian duct syndrome who experienced progressive degeneration of testicular tissue. In two, functional testicular tissue was still present some months after birth, but deteriortated progressively later. In one patient, testicular tissue was already absent at birth, but the normal virilization of external genitalia indicated that testicular degeneration must have occurred lat during fetal life, after the expected time of regression of male Müllerian ducts.Conclusion The high incidence of degeneration of testicular tissue in the presistent Müllerian duct syndrome could be indirectly linked to anatomical abnormalities which could favour testicular torsion, known to induce testicular regression.     

Assessment of physical activity and sleep by actigraphy: examination of gender differences

Research evidence suggests that actigraphy is a very important instrument in documenting sleep/wake patterns of people with a variety of sleep disorders or motor dysfunctions. The present actigraphic investigation examined physical activity and sleep profiles as a function of gender in volunteers monitored in their natural environment. Irrespective of age, women exhibited better sleep quality than did men. This was demonstrated by higher sleep efficiency index and lower frequency of transitions between sleep and wakefulness. Additionally, women slept more than men and had shorter sleep onset latency. However, no significant gender effect on daytime activity level and circadian activity amplitude was observed.     

Characterization and multiparameter analysis of visual adverse events in irofulven single-agent phase I and II trials.

PURPOSE: Irofulven (6-hydroxymethylacylfulvene) is a novel agent, derived from illudin S, with potent apoptotic effects in preclinical models. In the Phase I trial evaluating intermittent weekly schedules, visual symptoms were dose limiting. The aim of this analysis was to better characterize the visual adverse events of irofulven and provide treatment guidelines. EXPERIMENTAL DESIGN: Clinical data from 277 patients entered in single-agent Phase I to II clinical trials who received irofulven on days 1 and 15 every 4 weeks; days 1, 8, and 15 every 4 weeks; or days 1 and 8 every 3 weeks were included in this multiparameter analysis. RESULTS: Overall, 74 patients (27%) experienced visual symptoms. The most frequently reported symptoms were flashing lights (12% of patients), blurred vision (9%), and photosensitivity (8%). Grade 3 toxicity was observed in 12 patients (4%). The incidence and severity of visual events were dose dependent, with no grade 3 visual events occurring at doses < or =0.50 mg/kg and grade 1 to 2 events in only 12% and 8% of patients, at doses of < or =0.50 mg/kg and < or =20 mg/m2, respectively. Grade 1 to 2 toxicity was reversible in most patients. Abnormal electroretinogram and abnormal visual fields were noted after irofulven treatment in 24 of 39 patients (62%) and 15 of 26 patients (58%), respectively. All but 1 patient who had electroretinogram assessment received doses >0.50 mg/kg. Clinical examination and visual field assessment were found to be better correlated with symptoms and appear to be more appropriate for surveillance of irofulven retinal symptoms than electroretinograms. CONCLUSIONS: On the basis of retained antitumor activity and reversibility of grade 1 and 2 visual symptoms at lower doses, it appears that an irofulven dose of < or =0.50 mg/kg or < or =20 mg/m2, not to exceed 50 mg in a single dose, given as a 30-minute infusion on days 1 and 8 every 3 weeks or days 1 and 15 every 4 weeks minimizes the frequency and severity of visual symptoms.     

Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis.

PURPOSE: Radiation-induced fibrosis (RIF) is a rare morbid complication of radiotherapy, without an established method of management. RIF treatment with a combination of pentoxifylline (PTX) and alpha-tocopherol (vitamin E; Vit E) was recently prompted by the good results of a clinical trial and an animal study. The present double-blind, placebo-controlled, monocentric study was designed to assess the efficacy of this combination in treating RIF sequelae. PATIENTS AND METHODS: Twenty-four eligible women with 29 RIF areas involving the skin and underlying tissues were enrolled from December 1998 to April 2000. These patients, previously irradiated for breast cancer, were randomly assigned to four balanced treatment groups: (A) 800 mg/d of PTX and 1,000 U/d of Vit E; (B) PTX plus placebo; (C) placebo plus Vit E; and (D) placebo-placebo. The main end point measure was the relative regression of measurable RIF surface after 6 months of treatment. Assessment was completed by depth (with ultrasonography) and associated symptom measures. RESULTS: Twenty-two patients with 27 RIF areas were analyzed at 6 months. Mean RIF surface regression was significant with combined PTX/Vit E versus double placebo (60% +/- 10% v 43% +/- 17%; P =.038). The median slope for the speed of RIF surface area and volume regression was significantly higher for group A than groups B, C, and D. All treatments were well tolerated. CONCLUSION: Six months' treatment of combined PTX/Vit E can significantly reduce superficial RIF. Synergism between PTX and Vit E is likely, as treatment with each drug alone is ineffective, but these results require confirmation in larger series.