Melanomatous meningitis. Apropos of 3 cases

The meninges are frequently involved during the dissemination of malignant melanoma. This "meningeal melanoma" ranks fairly high on the list of metastatic meningites, side by side with meningeal carcinomatosis proper (i.e. related to a malignant epithelial tumour). Meningeal melanoma may be associated with a cerebral metastasis or isolated, as in the three cases reported here. Although its prognosis is sombre, its diagnosis is important since the possibilities of treatment are limited but exist. CASE-REPORTS: Case 1. This was a 68-year old woman who had initially presented with malignant melanoma in the maxillary region (SSM level IV, thickness 2.9 mm). Two years after the primary tumor was excised, secondary lesions developed in the lymph nodes and bones. A few weeks later, the patient fell into mental confusion progressing towards delusion of persecution. Neurological examination and CT scans were normal, but numerous melanoma cells were found in the CSF. This woman died one month after the first neurological signs had appeared. Case 2. This 63-year old man presented with bilateral axillary adenopathy and inflammatory thoracic plaques which at histology had proved to be metastases from a malignant melanoma of the shoulder surgically treated 10 years previously. After 14 months of almost complete remission under multiple chemotherapy (CPDD, ACTD, VDS), headaches and lumbosacral pain developed. Standard radiography and CT of the spine gave normal results, and it was only at the third lumbar puncture that the CSF was found to contain malignant cells. The patient died 2 months after the first neurological manifestations. Case 3. A 42-year old woman developed headaches and dysesthaesia in the arms and head. This was followed by oppositional semi-mutism. All exploratory examinations were normal, except for that of the CSF which showed 18 cells/mm3, 50 p. 100 of which were melanoma cells. The patient was transferred to the Dermatology department where he underwent excision of a left scapular melanoma difficult to classify (malignant blue naevus?). Combined treatment with Fotemustine* and DTIC produced an incomplete but relatively prolonged response. Death occurred after 8 months. DISCUSSION: A. Meningeal melanoma accounts for about 10 p. 100 of all metastatic meningites. The most frequent primary tumours in meningeal carcinomas are breast cancer and lung cancer. Malignant melanoma ranks third or fourth, but when the relative frequency of each of these three malignant diseases is taken into account, it appears that the risk of malignant melanoma is higher than that of any other solid tumour. B. In 410 cases extracted from the literature, the meninges were involved in 30 p. 100 of malignant metastatic melanomas found at autopsy. There is no publication that makes it possible to evaluate the relative frequency of melanomas affecting only the meninges or coexisting with cerebral metastases. This also applies to meningeal melanoma associated with non-neuro     

Sclerostin-Neutralizing Antibody Treatment Rescues Negative Effects of Rosiglitazone on Mouse Bone Parameters

Obesity, a growing pandemic, is a risk factor for many cancers and causes increased bone marrow adipose tissue (BMAT). in vitro studies and obese animal models suggest that BMAT contributes to cancer progression, but there is a lack of preclinical models to directly test BMAT's role in cancer. Overactivation of peroxisome-proliferator-activated receptor-γ (PPARγ) can skew bone formation and resorption rates, resulting in increased BMAT and trabecular bone loss. Thiazolidinediones (eg, rosiglitazone) are anti-diabetic therapies that promote adipogenesis through PPARγ activation. We investigated if rosiglitazone increases BMAT in an immunocompromised model, commonly used in cancer research, and if these effects could be reversed by co-administering a bone anabolic agent (sclerostin-neutralizing antibody [Scl-Ab]), which has been shown to inhibit adipogenesis, using DXA, μCT, OsO4 μCT, and dynamic histomorphometry. Four weeks of rosiglitazone in female SCID Beige mice (cohort 1) significantly decreased trabecular bone volume (BV/TV) by about one-half, through increased osteoclast and suppressed osteoblast activity, and significantly increased BMAT. In cohort 2, mice were administered rosiglitazone ± Scl-Ab for 4 weeks, and then rosiglitazone was discontinued and Scl-Ab or vehicle were continued for 6 weeks. Scl-Ab significantly increased bone parameters (eg, BV/TV, N.Ob/B.Pm, and MS/BS) in both groups. Scl-Ab also overcame many negative effects of rosiglitazone (eg, effects on trabecular bone parameters, increased mineralization lag time [MLT], and decreased bone formation rate [BFR]). Interestingly, Scl-Ab significantly decreased rosiglitazone-induced BMAT in the femur, mostly due to a reduction in adipocyte size, but had a much weaker effect on tibial BMAT. These data suggest targeting sclerostin can prevent rosiglitazone-induced bone loss and reduce BM adiposity, in some, but not all BMAT locations. Collectively, our data demonstrate that rosiglitazone increases BMAT in SCID Beige mice, but concomitant changes in bone may confound its use to specifically determine BMAT's role in tumor models. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Propofol anaesthesia reduces early post-operative emesis after paediatric strabismus surgery

Propofol anaesthesia may reduce postoperative emesis. The purpose of this study was to compare the incidence of emesis after propofol anaesthesia with and without nitrous oxide, compared with thiopentone and halothane anaesthesia, in hospital and up to 24 hr postoperatively, in outpatient paediatric patients after strabismus surgery. Seventy-five ASA class I or II, unpremedicated patients, aged 2–12 yr were randomly assigned to one of three groups: Thiopentone, 6.0 mg · kg^{? 1} iv induction followed by halothane and N₂O/O₂ for maintenance (T/H); propofol for induction, followed by propofol and oxygen for maintenance (P/O₂); and propofol for iv induction, followed by propofol infusion and N₂O/O₂ for maintenance (P/N₂O). All received vecuronium, controlled ventilation, and acetaminophen pr. Morphine was given as needed for postoperative analgesia. There were no differences in age, weight, number of eye muscles operated upon, duration of anaesthesia or surgery. The P/N₂O group (255 ± 80 μg· kg^{? 1}· min^{? 1}) received less propofol than the P/O₂ group (344 ± 60 μg · kg^{? 1}· min^{? 1}) (P ≤ 0.0001) and had shorter extubation (P < 0.001) and recovery (P < 0.01) times. Emesis in the hospital, in both the P/N₂O (4.0%) and P/O₂ group (4.0%) was less than in the T/H group (32%) (P < 0.01). Antiemetics were required in four patients in the T/H group (16.0%). Overall emesis after surgery was not different among the groups: T/H (48%), P/O₂ (28%) and P/N₂O (42%). The use of propofol anaesthesia with and without N₂O decreased only early emesis. This supports the concept of a short-acting, specific antiemetic effect of propofol.     

Transient enriched housing before amyloidosis onset sustains cognitive improvement in Tg2576 mice

Levels of educational and occupational attainment, as components of cognitive reserve, may modify the relationship between the pathological hallmarks and cognition in Alzheimer's disease (AD). We examined whether exposure of a Tg2576 transgenic mouse model of AD to environmental enrichment (EE) at a specific period during the amyloidogenic process favored the establishment of a cognitive reserve. We found that exposure to EE during early adulthood of Tg2576 mice—before amyloidogenesis has started—reduced the severity of AD-related cognitive deficits more efficiently than exposure later in life, when the pathology is already present. Interestingly, early-life exposure to EE, while slightly reducing forebrain surface covered by amyloid plaques, did not significantly impact aberrant inhibitory remodeling in the hippocampus of Tg2576 mice. Thus, transient early-life exposure to EE exerts long-lasting protection against cognitive impairment during AD pathology. In addition, these data define the existence of a specific life time frame during which stimulatory activity most efficiently builds a cognitive reserve, limiting AD progression and favoring successful aging.     

Performances,feasibility and acceptability of nasopharyngeal swab,saliva and oral-self sampling swab for the detection of severe acute respiratory syndrome coronavirus 2

European Journal of Clinical Microbiology & Infectious Diseases - Molecular diagnosis on nasopharyngeal swabs (NPS) is the current standard for COVID-19 diagnosis, but saliva may be an...     

Is sofosbuvir/ledipasvir safe for the hearts of children with hepatitis C virus?

Background

Symptomatic bradycardia has been reported in adults treated for chronic hepatitis C using sofosbuvir based regimens.

Cold-induced urticaria

Cold urticaria is characterized by the development of urticaria, usually superficial and/or angioedematous reaction after cold contact. It was found predominantly in young women. The diagnosis is based on the history and ice cube test. Patients with a negative ice cube test may have represented systemic cold urticaria (atypical acquired cold urticaria) induced by general body cooling. The pathogenesis is poorly understood. Cold urticaria can be classified into acquired and familial disorders, with an autosomal dominant inheritance. Idiopathic cold urticaria is most common type but the research of a cryopathy is necessary. Therapy is often difficult. It is essential that the patient be warned of the dangers of swimming in cold water because systemic hypotension can occur. H1 antihistamines can be used for treatment of cold urticaria but the clinical responses are highly variable. The combination with an H2 antagonists is more effective. Doxepin may be useful in the treatment. Leukotriene receptor antagonists may be a novel, promising drug entity. In patients who do not respond to previous treatments, induction of cold tolerance may be tried.