Uptake of iodine-123 MIBG by pheochromocytomas, paragangliomas, and neuroblastomas: a histopathological comparison

The percentage uptake of [123I]metaiodobenzylguanidine (MIBG) by tumors of the paraganglion system is compared with the number of neurosecretory granules (assessed by both light and electron microscopy) in the subsequently resected tumors in six patients. Iodine-123 MIBG was injected intravenously; the tumor uptake of [123I]MIBG varied between 0.001% and 0.14% of the injected dose per gram of tumor tissue at 22 hr. The number of neurosecretory granules in tissue sections was scored on a scale of I-III. A direct proportional correlation was found between the percentage uptake of [123I]MIBG by the tumor and the number of neurosecretory granules in the tissue sections but not with plasma or urinary catecholamines. This technique for imaging reflects the storage status of the tumor better than plasma and urinary catecholamine measurements.     

Hyperprolactinaemia and sexual function in the male

Although an uncommon cause of sexual dysfunction, hyperprolactinaemia is almost invariably associated with loss of libido and impotence in men. The finding of hyperprolactinaemia should prompt a systematic search for an underlying cause, particularly prolactin-secreting pituitary adenomas; in this condition, sexual dysfunction may antedate other complications of the pituitary tumour by many years.     

Analysis of a terminal Xp22.3 deletion in a patient with six monogenic disorders: implications for the mapping of X linked ocular albinism.

The molecular characterisation of chromosomal aberrations in Xp22.3 has established the map position of several genes with mutations resulting in diverse phenotypes such as short stature (SS), chondrodysplasia punctata (CDPX), mental retardation (MRX), ichthyosis (XLI), and Kallmann syndrome (KAL). We describe the clinical symptoms of a patient with a complex syndrome compatible with all these conditions plus ocular albinism (OA1). He has a terminal Xp deletion of at least 10 Mb of DNA. Both the mother and sister of the patient are carriers of the deletion and show a number of traits seen in Turner's syndrome. The diagnosis of ocular albinism was confirmed in the patient and his mother, who shows iris translucency, patches and streaks of hypopigmentation in the fundus, and macromelanosomes in epidermal melanocytes. By comparative deletion mapping we can define a deletion interval, which locates the OA1 gene proximal to DXS143 and distal to DXS85, with the breakpoints providing valuable starting points for cloning strategies.     

The music of speech: music training facilitates pitch processing in both music and language

The main aim of the present experiment was to determine whether extensive musical training facilitates pitch contour processing not only in music but also in language. We used a parametric manipulation of final notes' or words' fundamental frequency (F0), and we recorded behavioral and electrophysiological data to examine the precise time course of pitch processing. We compared professional musicians and nonmusicians. Results revealed that within both domains, musicians detected weak F0 manipulations better than nonmusicians. Moreover, F0 manipulations within both music and language elicited similar variations in brain electrical potentials, with overall shorter onset latency for musicians than for nonmusicians. Finally, the scalp distribution of an early negativity in the linguistic task varied with musical expertise, being largest over temporal sites bilaterally for musicians and largest centrally and over left temporal sites for nonmusicians. These results are taken as evidence that extensive musical training influences the perception of pitch contour in spoken language.     

Energy cost of running during a specific transition in duathlon]

The aim of the present study was to investigate the variability of the energy cost of running (Cr) during a simulated duathlon performed in outdoor conditions by elite duathletes. This duathlon consisted of 5 km of running, 30 km of cycling, and 5 km of running. The main result was the lack of significant difference in Cr between the two running bouts (210 +/- 10 mL d'O2.km-1.kg-1 vs. 217 +/- 10 mL d'O2.km-1.kg-1). This result is different from those observed during a triathlon, where an increase of energy cost of running bout has been reported. Furthermore, during a short-distance duathlon performed by well-trained subjects, none of the physiological (ventilation alteration, metabolic changes, or dehydration) or biomechanical factors that are classically evoked in triathlon research to explain Cr variability seem to be affected by the run-cycle-run transition. These results seem to minimize the negative effect of the cycle-to-run transition during a short-duration event in well-trained subjects.     

COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors

European Journal of Epidemiology - Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK...     

Phase I study of Datelliptium chloride,hydrochloride given by 24-h continuous intravenous infusion

Summary Datelliptium chloride, hydrochloride (SR 95 156B, NSC 626718X, DHE) was studied in a phase I trial of escalating doses given on a single 24-h continuous intravenous infusion schedule. Doses were escalated from 40 to 500 mg/m² in 19 patients who received a total of 24 courses. Courses were repeated after a minimal interval of 3 weeks. Local venous toxicity occurred at low doses (100 mg/m²) and was circumvented by the use of a central venous access for higher doses. Other clinical adverse events occurred (330 mg/m²), including moderate nausea and vomiting, mild diarrhea, dry mouth, neuropsychiatric manifestations, and fatigue. All of these side effects were reversible and none was dose-limiting. The dose-limiting toxicity was related to hepatic laboratory-test abnormalities in the form of reversible elevations of levels of serum bilirubin and liver enzymes at doses of 330 mg/m². The maximum tolerated dose for this schedule is 500 mg/m². Hematologic toxicity was minimal and non-dose-limiting. Neither drug-related deaths nor objective complete or partial responses were observed. However, a minor response and a long-term disease stabilization were obtained.     

Iatrogenic Thyrotoxicosis: Causal Circumstances, Pathophysiology, and Principles of Treatment—Review of the Literature

Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones. In most instances thyrotoxicosis is due to hyperthyroidism, a term reserved for disorders characterized by overproduction of thyroid hormones by the thyroid gland. Nevertheless, thyrotoxicosis may also result from a variety of conditions other than thyroid hyperfunction. The present report focuses on the etiologies, pathophysiology, and treatment of iatrogenic thyrotoxicosis. Iatrogenic thyrotoxicosis may be caused by (1) subacute thyroiditis (a result of lymphocytic infiltration, cellular injury, trauma, irradiation) with release of preformed hormones into circulation; (2) excessive ingestion of thyroid hormones (“thyrotoxicosis factitia”); (3) iodine-induced hyperthyroidism (radiologic contrast agents, topical antiseptics, other medications). Among these causes of iatrogenic thyrotoxicosis, that induced by the iodine overload and cytotoxicity associated with amiodarone represents a significant challenge. Successful management of amiodarone-induced thyrotoxicosis requires close cooperation between endocrinologists and endocrine surgeons. Surgical treatment may have a leading yet often underestimated role in view of the potential life-threatening severity of this disease, whereas others kinds of iatrogenic thyrotoxicosis are usually treated conservatively.     

Preclinical evaluation and structural optimization of anti-BCMA CAR to target multiple myeloma

Chimeric antigen receptor (CAR) T-cell based immunotherapy has become a promising treatment mainly for hematological malignancies. Following the major success of CD19-targeted CAR, new potential targets for other malignancies are required. As such, B-cell maturation antigen (BCMA) is an attractive tumor-associated antigen to be targeted in multiple myeloma (MM). Herein, we aimed at assessing the function and optimal configuration of different BCMA-specific CAR, based on the same targeting moiety but with a different hinge and co-stimulatory domain. We compared their function to that of a previously characterized BCMA-CAR used in clinical trials. All constructs were expressed at high levels by primary human T cells and could trigger cytokine production and cytotoxicity upon co-culture with multiple myeloma targets. Nonetheless, critical differences were observed in off-target activation, exhaustion, and activation marker expression and in vivo anti-tumoral activity mediated by these different constructs. Interestingly, we noted that CD8-based hinge, combined with a 4-1BB intracellular domain, proved superior compared to IgG4-connecting regions, and/or a CD28-signaling moiety respectively. Overall, this study emphasizes the influence of CAR primary structure on its function and led to the identification of a highly efficient BCMA-specific CAR, namely H8BB, which displayed superior anti-tumoral activity both in vitro and long-term in vivo efficacy.