Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized,double-blind,placebo-controlled study

Magnesium sulphate has been used in the acute treatment of migraines; some studies found it to be a highly effective medication in the acute control of migraine pain and associated symptoms. This randomized, double-blind, placebo-controlled study assesses the effect of magnesium sulphate on the pain and associated symptoms in patients with migraine without aura and migraine with aura. Sixty patients in each group were assigned at random to receive magnesium sulphate, 1000 mg intravenously, or 0.9% physiological saline, 10 ml. We used seven parameters of analgesic evaluation and an analogue scale to assess nausea, photophobia and phonophobia. In the migraine without aura group there was no statistically significant difference in the patients who received magnesium sulphate vs. placebo in pain relief. The analgesic therapeutic gain was 17% and number needed to treat was 5.98 at 1 h. There was also no statistical difference in relief of nausea. We did observe a significant lower intensity of photophobia and phonophobia in patients who received magnesium sulphate. In the migraine with aura group patients receiving magnesium sulphate presented a statistically significant improvement of pain and of all associated symptoms compared with controls. The analgesic therapeutic gain was 36.7% at 1 h. A smaller number of patients continued to have aura in the magnesium sulphate group compared with placebo 1 h after the administration of medication. Our data support the idea that magnesium sulphate can be used for the treatment of all symptoms in migraine with aura, or as an adjuvant therapy for associated symptoms in patients with migraine without aura.     

Migraine with aura versus migraine without aura: pain intensity and associated symptom intensities after placebo

OBJECTIVE: To compare the intensity of pain and associated symptoms after placebo administration in patients with migraine with aura and migraine without aura. BACKGROUND: Studies that evaluate drugs used in the acute treatment of migraine ideally should include a placebo arm. The International Headache Society also recommends stratification according to age and sex but not by the presence versus absence of aura. METHODS: The study was conducted as part of a placebo controlled randomized survey comparing four active drugs against placebo in the acute treatment of migraine. Patients were blinded as to treatment received. Placebo consisted of 10 mL of normal saline (0.9%) intravenously. Pain intensity was evaluated by a 10-point analogical-verbal scale. Nausea, photophobia, and phonophobia were evaluated by a four-point analogical-verbal scale. For statistical analysis, unpaired t-test with Welch correction was used. RESULTS: After placebo administration, reduction of symptom intensity (pain, nausea, photophobia, and phonophobia) in patients with migraine without aura was significantly greater than that observed in patients with migraine with aura. CONCLUSIONS: Our findings suggest that studies comparing placebo against an active drug should use stratification according to the presence versus absence of aura.     

Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model of multiple myeloma

Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients.     

Microglia are less pro‐inflammatory than myeloid infiltrates in the hippocampus of mice exposed to status epilepticus

Activated microglia, astrogliosis, expression of pro‐inflammatory cytokines, blood brain barrier (BBB) leakage and peripheral immune cell infiltration are features of mesial temporal lobe epilepsy. Numerous studies correlated the expression of pro‐inflammatory cytokines with the activated morphology of microglia, attributing them a pro‐epileptogenic role. However, microglia and myeloid cells such as macrophages have always been difficult to distinguish due to an overlap in expressed cell surface molecules. Thus, the detrimental role in epilepsy that is attributed to microglia might be shared with myeloid infiltrates. Here, we used a FACS‐based approach to discriminate between microglia and myeloid infiltrates isolated from the hippocampus 24 h and 96 h after status epilepticus (SE) in pilocarpine‐treated CD1 mice. We observed that microglia do not express MHCII whereas myeloid infiltrates express high levels of MHCII and CD40 96 h after SE. This antigen‐presenting cell phenotype correlated with the presence of CD4^pos T cells. Moreover, microglia only expressed TNFα 24 h after SE while myeloid infiltrates expressed high levels of IL‐1β and TNFα. Immunofluorescence showed that astrocytes but not microglia expressed IL‐1β. Myeloid infiltrates also expressed matrix metalloproteinase (MMP)?9 and 12 while microglia only expressed MMP‐12, suggesting the involvement of both cell types in the BBB leakage that follows SE. Finally, both cell types expressed the phagocytosis receptor Axl, pointing to phagocytosis of apoptotic cells as one of the main functions of microglia. Our data suggests that, during early epileptogenesis, microglia from the hippocampus remain rather immune supressed whereas myeloid infiltrates display a strong inflammatory profile. GLIA 2016 GLIA 2016;64:1350–1362     

Outcomes of total hip replacement in patients with slipped capital femoral epiphysis

Background

Total hip replacement has been advocated for the treatment of degenerative hip diseases secondary to slipped capital femoral epiphysis; nonetheless, outcomes of this procedure have not been well established. We reviewed the outcomes of modern total hip replacements in patients who suffered from slipped capital femoral epiphysis.

Methods

A retrospective study was carried out on 32 total hip replacements performed on 28 patients who suffered from slipped capital femoral epiphysis from August 1994 to January 2007. The average age at the time of surgery was 45?years. Clinical evaluation was performed using the Harris Hip Score, radiographic assessment measuring cup and stem orientation, the extent of osteolysis around the implant, and leg length discrepancy. The average follow-up was 98?months (range 25–204?months).

Results

Two total hip replacements failed, one for stem aseptic loosening and the other for modular neck failure. The cumulative survival rate at 9?years was 92.8?%. If the end point was revision for implant loosening, the survival rate improved to 96.8?% at 9?years. The only complication recorded was an intraoperative fracture of the lesser trochanter immediately treated with cerclage wire. At the latest follow-up, the Harris Hip Score averaged 86 (range 70–97). Leg length discrepancies greater than 1?cm were present in 18 cases before surgery, and in only 6 cases after surgery.

Discussion

We recommend total hip replacement for patients who suffer from slipped capital femoral epiphysis because of the satisfactory survival, low complication rate, and the possibility of restoring leg length.     

The generality of the stimulus-binding hypothesis across drinking behavior and task performance in alcoholics

This experiment investigated the validity of applying the stimulus-binding hypothesis of obesity to conceptualize drinking and task performance behaviors in alcoholics. Twenty alcoholics and 12 nonalcoholics participated in two counterbalanced experimental sessions. One session involved an assessment of subjects' voluntary consumption of preferred and nonpreferred nonalcoholic beverages. The other session involved their performance of four tasks that involved or manipulated the presence of salient external cues. The prediction of heightened externality in alcoholics was supported on the beverage consumption measures and was marginally supported on the task performance measures. The results are discussed in terms of their implications for models and treatments of alcohol problems.     

Migraine in the elderly: a comparison with migraine in young adults

OBJECTIVE: In this study we compare the clinical features of migraine attacks occurring in the elderly (60 to 70 years) and in younger migraineurs (20 to 40 years). BACKGROUND: Studies comparing the clinical features of migraine at different ages are still lacking. These studies are important for a better comprehension of the natural history of migraine, as well as to refine our recognition of the disease. METHODS: We retrospectively assessed subjects seen from 1995 to 2000 in a university-based outpatient headache clinic in Brazil. We reviewed 144 charts from patients 60 to 70 years (mean = 66.4). We applied a questionnaire based on the first edition of the International Classification of Headache Disorders (criteria for episodic migraine remained unchanged in the second edition). Controls were migraineurs from 20 to 40 years (mean = 32.6). RESULTS: Migraine occurred in 25% of the elderly and 29% of younger migraineurs (NS). A lower proportion of migraine attacks in the elderly were unilateral (38% vs. 57%, P < .01), or with associated symptoms (nausea = 75% vs. 86%, P = .05; vomiting = 30% vs. 54%, P < .05, photophobia and phonophobia = 83% vs. 94%, P < .05). Other symptoms such as paleness (P = .0441), dry mouth (P = .0093), and anorexia (P = .05) were more common in the elderly. CONCLUSION: Migraine is less typical in the elderly and more frequently associated with vegetative symptoms. Therefore, the diagnosis of migraine in elderly subjects may be more challenging, and many seniors with this primary headache can be misdiagnosed.     

The role of the occupational health physician in smoking cessation programmes: the experience of the "Clinica del Lavoro" of Milan

. BACKGROUND: The "Centre for the prevention, diagnosis and treatment of tobacco dependency", set up at the Occupational and Environmental Respiratory Diseases Section of the Clinica del Lavoro in Milan in September 2000, can count on multidisciplinary expertise, including occupational health physicians, pneumologists and clinical psychologists. Each step of the diagnostic and therapeutic process is based on an integrated approach that considers both the biological aspects of tobacco dependency and the psychological and behavioural aspects. The Centre, moreover, within the framework of "Health Promotion" programmes, offers advice to businesses as regards the new legislation that prohibits smoking at the workplace. METHODS: The proposed treatment programme is based on psychological and motivational support (personal or team work), that can be associated with pharmacological therapy, either as an alternative or an addition. The drug preferred is slow-releasing buproprione, which has proved to be extremely effective compared to other drugs in increasing the probability of smoking cessation and decreasing side effects. RESULTS: In an occupational population of more than 2000 workers, we succeeded in treating about 51% of the subjects, who had stopped smoking, after one year from the beginning of the programme. The best results were achieved using the association of psychological support and buproprione therapy (54%), compared with the other methods (psychological support alone: 42%; psychological support and free nicotine replacement therapy: 33%).