A comparative safety review of histone deacetylase inhibitors for the treatment of myeloma

Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.

Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.

Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity.     

The Effect of Helicobacter pylori on Gastric Cancer Treated with Adjuvant Chemotherapy After Curative Resection

Helicobacter pylori has been associated with diverse pathologies of varying severity. We investigated the H. pylori infection status and its association with the pathologic features and clinical outcomes in stage III gastric cancer patients treated with adjuvant therapy after curative resection. Between 2004 and 2009, the records of 76 consecutive patients were retrospectively reviewed. H. pylori infection was confirmed by examination of pathological specimen. The relationship between H. pylori and the clinicopathological features was analyzed by Fisher exact test, Student’s t test, and Kaplan-Meier method. Of the 76 patients, 16 patients (21.1 %) were confirmed for H. pylori infection. The median age was 59 years. Twenty-three patients received chemotherapy and remainder received chemoradiotherapy. H. pylori status did not correlate with the clinicopathologic features. It was greater in non-neoplastic tissue than the tumor tissue (21.1 vs 7.9 %). Median follow-up was 21 months. During this period, 88.2 % patients had experienced tumor recurrence, and 85.5 % patients had died. Recurrence was observed in 87.5 % patients and in 88.3 % patients in H. pylori-positive and H. pylori-negative patients, respectively (P = 0.92). Disease-free survival was 28.4 ± 7.9 months and overall survival was 31.5 ± 7.4 months in H. pylori-positive patients compared with 28.3 ± 3.7 and 33.2 ± 3.4 months, respectively, in H. pylori-negative patients. H. pylori infection status did not have effect on the overall or disease-free survival (p = 0.85 and P = 0.86), respectively. H. pylori status might not be useful as a prognostic and predictive factor for clinical outcomes.     

Adhesive fragment reattachment after orthodontic extrusion: a case report

Abstract –  In the treatment of crown fractures, adhesive fragment reattachment provides a good alternative to other restorative techniques, offering several advantages. The present paper reports a case in which the treatment of a cervical crown fracture was accomplished by reattaching the tooth fragment with a flowable resin composite. Orthodontic root extrusion was performed with a modified Hawley appliance prior to fragment reattachment. The clinical and radiographic results after 2.5 years were successful.     

Midazolam in treatment of various types of seizures in children

Midazolam is a recently developed water-soluble benzodiazepine that shares anxiolytic, muscle relaxant, hypnotic and anticonvulsant actions with other members of this class. There are limited studies that midazolam can be used successfully to treat seizures in adults and children. In this study, 0.2 mg/kg intramuscular (IM) midazolam was administered to 11 children (eight boys and three girls), aged 3 days to 4 years (mean age 1.8±1.4 years), with seizures of various types. In all but one child, seizures stopped in 15 s–5 min after injection. No side effects were observed. These results suggest that IM administration of midazolam may be useful in a variety of seizures during childhood, especially in case of intravenous (IV) line problem.     

Vascular lesions in Beh?et's disease

Vascular lesions in Beh?et's disease are generally localized in the venous system: up to 24% of the cases reported in the literature are accompanied by thrombosis/thrombophlebitis. Reports of arterial involvement are rare but have increased during the last decade. Surgical treatments of arterial aneurysms and occlusions are often followed by recurrences due to progression or relapses of the inflammatory vessel wall lesions. Aneurysms of the pulmonary artery are rare. They may be complicated by thrombosis within the aneurysm and massive hemoptysis due to bronchial erosion and formation of an arterio-bronchial fistula. 27 cases of Beh?et's disease are reported.     

Preliminary findings for preemptive analgesia with inhaled morphine: efficacy in septoplasty and septorhinoplasty cases.

OBJECTIVE: The aim of this study was to assess the efficacy of inhaled morphine for preemptive analgesia in patients who undergo septoplasty or septorhinoplasty. STUDY PLAN AND METHODS: Eighty ASA I-II patients scheduled for septoplasty or septorhinoplasty were recruited and randomly divided into 2 groups that received different treatments 10 minutes prior to induction. The preemptive analgesia group (Group P, n = 40) received 65 mug kg(-1) morphine sulphate (a 3-mL volume) via an oral nebulizer, and the control group (Group C, n = 40) received 3 mL 0.9% sodium chloride (physiological saline) via the same type of nebulizer. Blood pressure, oxygen saturation, heart rate, time to first requirement for analgesia, and occurrence of nausea/vomiting were recorded. RESULTS: There were no significant differences between Groups P and C with respect to age, body weight, sex distribution, or duration of surgery. There was also no significant difference between the group frequencies of postoperative nausea/vomiting. The time to first requirement for analgesia was significantly longer in Group P than Group C. CONCLUSION: The results of this preliminary study suggest that a single dose of inhaled morphine administered preemptively prior to septoplasty or septorhinoplasty provides effective postoperative analgesia. EBM rating: B-3b.     

Chlamydial infections and male infertility

Chlamydial infections may be difficult to diagnose due to the silent symptoms and difficulty in culturing. An infectious process may impair fertility by adversely affecting sperm functions, resulting in testicular damage or causing obstruction of the genital tract. In our study, we tried to find Chlamydial antigen by using EIA (Enzyme Immune Assay) and to compare the Ag(+) and Ag(−) groups according to semen parameters. Except for semen volume, we found significant differences in density, morphology, motility and viability (intervolume p>0.05, interdensity p<0.01, intermorphology p<0.001, intermotility p<0.001 and interviability p<0.001).     

Assessment of changes in regional cerebral blood flow in patients with major depression using the 99mTc-HMPAO single photon emission tomography method

Regional cerebral blood flow was investigated in 14 patients with major depression diagnosed according to the DSM-III-R criteria (six patients with single and eight patients with recurrent episodes) and in ten healthy volunteers. The mean ages of the patients and the controls were 33.5 ± 2.7 and 31.6 ± 2.6 years, respectively. The severity of the depression was assessed using the 17-item Hamilton Depression Scale (mean: 23.2 ± 1.5). None of the patients was under medication. After administration of 500 MBq technetium-99m hexamethylpropylene amine oxime, a single photon emission tomography study was performed and then transaxial, sagittal and coronal slices were obtained. For the semiquantitative analysis of the data, the ratios of the mean counts/pixel to the whole slice were calculated for 24 regions on three consecutive transaxial slices in the orbitomeatal plane. Additionally, left/right and frontal/occipital ratios were calculated. Both sides of the temporal region had a significantly decreased cerebral blood flow (CBF) when compared to the controls. The left/right ratio of the prefrontal region was also significantly lower in the patients than in the controls. The Hamilton score had a negative correlation with blood flow in the anterofrontal and left prefrontal regions. According to our results, regional CBF seems to be decreased in the left prefrontal and in both temporal regions in major depression. The severity of depression is correlated with the reduction in CBF in the regions of the anterofrontal and left prefrontal cortex.     

Effect of Nitroglycerin Inhalation on Patients with Pulmonary Hypertension Undergoing Mitral Valve Replacement Surgery

Background: The aim of this study was to investigate the postoperative hemodynamic effects of nitroglycerin inhalation on patients with pulmonary hypertension undergoing mitral valve replacement surgery.

Methods: Twenty patients who underwent mitral valve replacement surgery were included in the study. In the surgical intensive care unit, at T0 (before the inhalation of nitroglycerin), basal systemic and pulmonary hemodynamics were recorded. Then, 2.5 [mu]g [middle dot] kg-1 [middle dot] min-1 nitroglycerin liquid nebulized by a 2-l gas flow of 40% oxygen and air mixture was administered to the patients who were diagnosed as having pulmonary hypertension (mean pulmonary arterial pressures > 25 mmHg). The same parameters were measured at the first (T1), third (T2), and fifth (T3) hours after the beginning of this treatment and 1 h after the end of nitroglycerin inhalation (T4).

Results: There were no statistically significant differences at T0, T1, T2, T3, or T4 with respect to heart rate, mean arterial pressure, systemic vascular resistance, cardiac index, mixed venous oxygen saturation, arteriovenous oxygen content difference, or arterial carbon dioxide tension. However, mean pulmonary artery pressure, pulmonary vascular resistance, and intrapulmonary shunt fraction were significantly lower, and the arterial oxygen tension/fraction of inspired oxygen ratio was higher at T1, T2, and T3 when compared to that of T0 and T4.