Serum ionized magnesium and calcium levels in adult patients with seizures

Objective. Prior studies have been equivocal about whether or not serum levels of the divalent ions calcium and magnesium are altered during different types of seizures. Magnesium is a potential modulator of seizure activity because of its ability to antagonize the excitatory calcium influx through the N‐methyl‐D‐aspartate (NMDA) receptor. We hypothesize that serum ionized levels of calcium (Ca²⁺) and magnesium (Mg²⁺) would be altered significantly during certain types of seizures. Material and methods. A convenience sample of seizure patients presenting to an emergency department (ED) were enrolled in this prospective study. Novel ion‐selective electrodes were used to measure Ca²⁺ and Mg²⁺. Data were reported as mean values±standard deviations. Group comparisons were analyzed by ANOVA with post‐hoc testing using the Bonferroni, or the Fisher exact test, where appropriate, α = 0.05 (two‐tailed). Results. Forty‐nine patients with seizure and 32 healthy racially matched controls were included in the study. Seizure patients had a significantly (p<0.001) lower mean Mg²⁺, but not total serum Mg and a significantly (p<0.001) higher Ca²⁺/Mg²⁺ ratio than that in controls. Conclusions. We were able to show significantly lower Mg²⁺ and higher ionized Ca²⁺/Mg²⁺ ratios in seizure patients compared with a racially matched control group.     

Hodgkin disease: CT of the thymus

The computed tomography (CT) scans in two groups of patients with Hodgkin disease were reviewed to determine the frequency of thymic enlargement. In 50 CT scans from 50 patients with evidence of thoracic disease on CT scans who were examined for primary staging, the thymus was enlarged in 15 of 50 (30%). Fifty CT scans were obtained from 44 patients at the time of 50 separate episodes of known or suspected relapse. Relapse occurred in the mediastinum in 12 episodes, lung parenchyma in five, and both sites in one. Thymic enlargement thought to be due to involvement by disease was present in seven of 18 (38%). Mediastinal disease was associated with thymic enlargement in all but one patient in whom a thymic cyst developed after radiation therapy. Differentiation of thymic enlargement from enlarged superior mediastinal lymph nodes was easily made in all but two patients. Thymic enlargement in the absence of lymph node enlargement may indicate a different disease, since isolated Hodgkin disease of the thymus is uncommon. Primary thymic tumor should be considered initially, whereas after treatment, rebound hyperplasia of the thymus may be the cause of enlargement.     

Three-question set from Michigan Neuropathy Screening Instrument adds independent prognostic information on cardiovascular outcomes: analysis of ALTITUDE trial

Aims/hypothesis

The self-administered Michigan Neuropathy Screening Instrument (MNSI) is used to diagnose diabetic peripheral neuropathy. We examined whether the MNSI might also provide information on risk of death and cardiovascular outcomes.

Methods

In this post hoc analysis of the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial, we divided 8463 participants with type 2 diabetes and chronic kidney disease (CKD) and/or cardiovascular disease (CVD) into independent training (n = 3252) and validation (n = 5211) sets. In the training set, we identified specific questions that were independently associated with a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction/stroke, heart failure hospitalisation). We then evaluated the performance of these questions in the validation set.

Results

In the training set, three questions (‘Are your legs numb?’, ‘Have you ever had an open sore on your foot?’ and ‘Do your legs hurt when you walk?’) were significantly associated with the cardiovascular composite outcome. In the validation set, after multivariable adjustment for key covariates, one or more positive responses (n = 3079, 59.1%) was associated with a higher risk of the cardiovascular composite outcome (HR 1.54 [95% CI 1.28, 1.85], p < 0.001), heart failure hospitalisation (HR 1.74 [95% CI 1.29, 2.35], p < 0.001), myocardial infarction (HR 1.81 [95% CI 1.23, 2.69], p = 0.003), stroke (HR 1.75 [95% CI 1.20, 2.56], p = 0.003) and three-point major adverse cardiovascular events (MACE) (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) (HR 1.49 [95% CI 1.20, 1.85], p < 0.001) relative to no positive responses to all questions. Associations were stronger if participants answered positively to all three questions (n = 552, 11%). The addition of the total number of affirmative responses to existing models significantly improved Harrell’s C statistic for the cardiovascular composite outcome (0.70 vs 0.71, p = 0.010), continuous net reclassification improvement (+22% [+10%, +31%], p = 0.027) and integrated discrimination improvement (+0.9% [+0.4%, +2.1%], p = 0.007).

Conclusions/interpretation

We identified three questions from the MNSI that provide additional prognostic information for individuals with type 2 diabetes and CKD and/or CVD. If externally validated, these questions may be integrated into the clinical history to augment prediction of CV events in high-risk individuals with type 2 diabetes.

     

Infection rates in sterile males of morsitans, palpalis and fusca groups Glossina for pathogenic Trypanosoma species from East and West Africa

Infection rates in sterile male Glossina morsitans centralis, G. austeni, G. palpalis palpalis, G.p. gambiensis, G. fuscipes fuscipes, G. tachinoides and G. brevipalpis for Trypanosoma vivax, T. congolense and T. brucei isolated from East and West Africa, were studied. Five groups of the sterile males, together with the five groups of sexually fertile males, of each of the respective species and subspecies were allowed to feed for 24 days on a Boran calf or goats infected with T. vivax or T. congolense, or with T. brucei for 34 days, after which they were dissected. The results showed that the infection of the pathogenic Trypanosoma species became better established in some tsetse species than in others. Also, the infection rates of T. vivax, T. congolense and T. brucei for sterile and sexually fertile males of any of the above Glossina did not differ significantly. These results indicate that releases of sterile male tsetse in the tsetse control programme will potentially increase the risk of trypanosomiasis during the period of tsetse releases in the affected areas, unless in the areas with low tsetse density the sterile male tsetse are rendered refractory to trypanosome infection prior to their releases while in the areas with medium to high tsetse densities, the resident tsetse populations are initially reduced with insecticides, traps and/or targets.     

Thyrotoxicosis during sunitinib treatment for renal cell carcinoma

Context Sunitinib malate is an oral tyrosine kinase inhibitor used in the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumours. Hypothyroidism has been observed in patients treated with sunitinib, but the mechanism whereby sunitinib induces hypothyroidism is unknown. Objective To describe a series of six patients who developed thyrotoxicosis while on sunitinib for metastatic RCC. Setting The study was conducted at Austin Health, a tertiary teaching hospital in Melbourne, Australia. Results Two patients developed severe thyrotoxicosis within 10 weeks after commencing sunitinib. In contrast, in the four patients who presented with later onset (16–30 weeks) thyrotoxicosis, the thyrotoxicosis was relatively mild, self‐limiting and rapidly progressed to hypothyroidism. These patients experienced recurrent episodes of thyrotoxicosis in temporal relation to their cyclical sunitinib treatment. One patient had cytological evidence of lymphocytic thyroiditis. Conclusions These findings suggest that sunitinib‐induced hypothyroidism may be a consequence of preceding thyroiditis with associated transient thyrotoxicosis. As predictive factors are currently unknown, we suggest regular monitoring of thyroid function in all patients commenced on sunitinib. Clinicians treating patients with sunitinib or other similar kinase inhibitors should to be alerted to thyroid dysfunction as a potential toxicity of these agents.     

Initiation of the extrinsic pathway of coagulation by human and rabbit alveolar macrophages: a kinetic study

We examined assembly and expression of the factor X activating complex on human and rabbit alveolar macrophages. Kinetic parameters of the factor X activating reaction were determined by functional titrations of factors VII and X with macrophage tissue factor (TF) added. We found rapid activation of factor X to Xa on alveolar macrophage surfaces. Detection of rapid factor Xa formation on macrophages required addition of exogenous factors VII and X. At plasma concentrations of the purified factors, factor Xa was formed on freshly isolated macrophages at approximately 5.4 pmol/min/10(6) cells. After macrophage maturation in culture for 20 hours with LPS (endotoxin) added, the factor X activation rate was increased two- to sixfold. The km' (apparent km) of TF-factor VII enzymatic complexes assembled on alveolar macrophages for factor X were (258 +/- 55 and 475 +/- 264 nmol/L for human and rabbit cells, respectively). The km' did not change during macrophage maturation in culture, but V'max (apparent Vmax) was consistently increased. The K1/2 of human factor VII (concentrations giving half maximal rates of factor X activation) for the interaction with human and rabbit alveolar macrophage TF were 0.191 +/- 0.096 and 1.7 +/- 0.7 etamol/L, respectively. The K1/2 were not significantly changed after maturation, whereas rates of Xa formation at saturation with factor VII were increased. The fast rates of factor X activation observed at physiologic concentrations of plasma-derived factors VII and X indicate that TF on alveolar macrophages is likely to provide sites for binding of factor VII and activation of factor X in vivo during clotting reactions associated with alveolar edema and inflammation.