Intravenous Immunoglobulin and Rituximab for Cerebellar Ataxia with Glutamic Acid Decarboxylase Autoantibodies

Cerebellar ataxia associated with glutamic acid decarboxylase autoantibodies (GAD-ab) is a rare and usually slow progressive disease with moderate to severe gait and limb ataxia, dysarthria, and nystagmus. The treatment for this condition is still being discussed. We report the cases of three patients with GAD-ab cerebellar ataxia treated successively with intravenous immunoglobulin (IVIg) and rituximab. Symptoms improved in one case after rituximab therapy and were stabilized in another after a combined therapy of IVIg and rituximab. The third patient continued to worsen despite these treatments. We conclude that IVIg and rituximab therapy could improve or stabilize GAD-ab cerebellar ataxia. Early treatment, the lack of cerebellar atrophy on magnetic resonance imaging, and a subacute onset of the symptoms could be decisive prognostic factors.     

Men Who Have Sex with Mens’ Exposure to,Use of,and Subjective Experiences with the ‘NYC Condom’

In 2007, the New York City (NYC) Department of Health introduced the ‘NYC Condom’—a Lifestyles^® condom with a ‘NYC’ logo. Few studies have evaluated attitudes toward or distribution of the ‘NYC Condom’ among men who have sex with men (MSM)—a population at increased risk for HIV/STIs. 148 MSM completed a survey about their exposure to, use of, and experiences using the ‘NYC Condom.’ The majority (93.2 %) had seen the ‘NYC Condom;’ 82.4 % of said men had used it. Among MSM who used it, 82.1 % rated it average or above. Exposure did not statistically differ by race/ethnicity, HIV status, gay or barebacker identification, or sex role. Use was neither significantly associated with demographic characteristics nor recruitment source, suggesting distributional success in reaching various sub-populations of MSM. Among those who had not used the ‘NYC Condom,’ 22.2 % reported size or quality concerns, suggesting a demand for alternative prevention campaigns.     

Long-term decrease in Na,K-ATPase activity after pilocarpine-induced status epilepticus is associated with nitration of its alpha subunit

Temporal lobe epilepsy (TLE) is the most common type of epilepsy with about one third of TLE patients being refractory to antiepileptic drugs. Knowledge about the mechanisms underlying seizure activity is fundamental to the discovery of new drug targets. Brain Na⁺,K⁺-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. In the present study we tested the hypothesis that decreased Na⁺,K⁺-ATPase activity is associated with changes in the alpha subunit phosphorylation and/or redox state. Activity of Na⁺,K⁺-ATPase decreased in the hippocampus of C57BL/6 mice 60 days after pilocarpine-induced status epilepticus (SE). In addition, the Michaelis–Menten constant for ATP of α2/3 isoforms increased at the same time point. Nitration of the α subunit may underlie decreased Na⁺,K⁺-ATPase activity, however no changes in expression or phosphorylation state at Ser⁹⁴³ were found. Further studies are necessary define the potential of nitrated Na⁺,K⁺-ATPase as a new therapeutic target for seizure disorders.     

Ischemic stroke in prediabetic patients

To describe the clinical characteristics of first-ever ischemic stroke (IS) patients with prediabetes, and to compare them with diabetes mellitus (DM) and non-DM patient characteristics. Retrospective analysis of a prospective series of first-ever acute IS patients. Patients were classified as non-DM (HbA1c during admission <5.7 % and no previous evidence of 2 or more fasting glucose >126 mg/dL), prediabetes (HbA1c from 5.7 to 6.4 %), and DM (previous DM diagnosis or HbA1c ≥6.5 % independently of current blood glucose). Demographic and clinical characteristics were compared between the three groups, along with outcome data [early neurological deterioration (END), 3-month poor outcome, 3-month mortality, outcome after rtPA treatment]. No demographic differences were observed. Prediabetic patients had more arterial hypertension (p = 0.006) and higher waist circumference (p < 0.0001) than non-DM patients, and DM patients had more hypercholesterolemia (p < 0.0001), body mass index (p = 0.017), and coronary artery disease (p = 0.005) than prediabetics. There were differences in TOAST subtype distribution (p < 0.0001). There were no differences in rtPA treatment success rate between groups. Multivariate analysis adjusted by age and stroke severity showed that DM but not prediabetes is an independent factor associated with END and 3-month poor outcome. Prediabetic patients with IS exhibit an “intermediate” vascular risk factor profile between that of non-DM and DM patients. In contrast to DM patients, IS prognosis in patients with prediabetes is similar to non-DM patients.     

The Brazilian Founder Mutation TP53 p.R337H is Uncommon in Portuguese Women Diagnosed with Breast Cancer

Since the first studies reporting the TP53 p.R337H mutation as founder mutation in Southern and Southeastern Brazil, there has been controversy on its origin. Preliminary analysis of a small subset of Brazilian mutation carriers revealed that the haplotype incided on a Caucasian background. The vast majority of carriers identified today reside in Brazil or, if identified in other countries, are Brazilian immigrants. To our knowledge, the only two exceptions of carriers without a recognizable link with Brazil are two European families, from Portugal and Germany. Haplotype analysis in the Portuguese family revealed the same haplotype identified in Brazilian individuals, but in the German family, a distinct haplotype was found. Knowing that a significant proportion of women with breast cancer (BC) in Southern Brazil are p.R337H carriers, we analyzed p.R337H in a Portuguese cohort of women diagnosed with this disease. Median age at diagnosis among the first 573 patients tested was 60 years and 100 (17.4%) patients had been diagnosed at or under the age of 45 years. Mutation screening failed to identify the mutation in the 573 patients tested. These results are in contrast with the mutation frequency observed in a study including 815 BC‐affected women from Brazil, in which carrier frequencies of 12.1 and 5.1% in pre‐ and postmenopausal women were observed, respectively. These findings suggest that the Brazilian founder mutation p.R337H, the most frequent germline TP53 mutation reported to date, is not a common germline alteration in Portuguese women diagnosed with BC.     

All-trans-retinoic acid counteract the tumor-stimulating effect of hepatectomy and increases survival of rats bearing liver metastases

Background

We previously demonstrated a stimulating effect of hepatectomy on residual tumor cells after resection of liver metastases. The aim of this study was to analyze the effect of all-trans-retinoic acid (ATRA) on the protumor effect of hepatectomy and survival of hepatectomized rats bearing liver metastases. We also explored whether ATRA interfered with the tumor promoting effect of hepatotropic growth factors (GFs).

Methods

The in vitro effect of ATRA on proliferation of S4MH rhabdomyosarcoma tumor cells was assessed when cultured with laparotomized or hepatectomized rat serum (HRS), or in the presence of GFs (hepatocyte growth factor, insulin growth factor 2, Platelet Derived Growth Factor (PDGF)-BB, and vascular endothelial growth factor). For the in vivo studies, rats were partially hepatectomized on day 10 after metastasis induction, one group being treated with ATRA from day 7 to 14, and a second receiving cyclophosphamide (CY; on days 10 and 14) alone or with ATRA. We determined the size and number of liver and lung metastases. Finally, we analyzed the effect of treatments on rat survival.

Results

Hepatotropic GFs increased cell proliferation in a similar manner to HRS. In vitro, ATRA blocked the protumor effect of both HRS and GFs. In vivo, ATRA reduced the size and number of liver and lung metastases, and significantly increased rat survival. Furthermore, adding ATRA to CY significantly increased survival compared with CY alone.

Conclusions

In our model, ATRA minimizes the tumor-stimulating effect of hepatectomy, reducing the number and size of liver metastases and improving survival. The results suggest that the ATRA may be useful for blocking the growth-promoting effect of hepatotropic GFs released after liver metastasis resection.     

Genetic Expression Profile of Human Liver Grafts in Ischemia-Reperfusion Injury: Comparison of Familial Amyloidotic Polyneuropathy and Deceased-Donor Liver Grafts

This study aimed to compare the histologic and molecular gene expression at several surgical times (beginning of harvesting, T0; end of cold ischemia period, T1; and after reperfusion, T2) to characterize the ischemia-reperfusion injury (IRI) in deceased-donor liver grafts harvested from patients with familial amyloidotic polyneuropathy (FAP). For this purpose, 54 patients undergoing liver transplantation were studied and divided into 3 groups: deceased donor to cirrhotic recipient (group 1; n = 27), deceased donor to FAP recipient (group 2; n = 15), and FAP donor to cirrhotic recipient (group 3; n = 12). The main comparison was performed between a histologic score (Suzuki score, adding steatosis and neutrophil infiltration), and molecular gene expression of the following genes: interleukin (IL) 1β, IL-6, E-selectin, Fas-ligand, granzyme B, heme oxygenase 1 (HO1), and nitric oxide synthetase (iNOS2A). We observed less neutrophil infiltration levels in group 3 in sample T0 (P = .0082), which was associated with gene expression of HO1 in the biopsies at T2 (P = .022). In group 3, the molecular expression of genes related to attenuated proinflammatory reaction during IRI, iNOS2A at T0 and HO1 at T2, was detected. We conclude that FAP liver grafts express differently the genes associated with an attenuated proinflammatory reaction, presenting less neutrophil infiltration at harvesting. These findings add more knowledge about the better short-term outcomes in patients receiving this type of liver graft.