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.     

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 N-acetylcysteine on blood and tissue lipid peroxidation in lipopolysaccharide-induced obstructive jaundice.

In obstructive jaundice, free radical production is increased and antioxidative activity is reduced. N-Acetylcysteine (NAC) has a beneficial effect with anti-inflammatory and antioxidant activity, acting as a free radical scavenger. NAC inhibits inducible nitric oxide synthase, suppresses cytokine expression/release, and inhibits adhesion molecule expression and nuclear factor kappa B. The aim of this study was to investigate the effects of NAC on liver/renal tissue and serum lipid peroxidation in lipopolysaccharide (LPS)-induced obstructive jaundice. We randomized 60 rats into 6 groups: group 1, Sham; group 2, obstructive jaundice (OJ) induced after bile-duct ligation; group 3, OJ + NAC (100 mg kg- 1 subcutaneously); group 4, OJ + LPS (10 mg kg-1); group 5, OJ + NAC + LPS; and group 6, OJ + LPS + NAC. For each group, the biochemical markers of lipid peroxidation and the antioxidant products were measured in serum and liver/renal tissue after sacrifice. Almost all lipid peroxidation products levels were increased and antioxidant products levels were decreased in groups who received LPS (groups 4, 5, and 6), but the effect was less remarkable when NAC was administered before LPS (group 5). The same trend was seen for groups with OJ +/- LPS who did not received NAC or received it after induced toxemia (groups 2, 4, and 6) as compared to groups 1 and 3. Moreover, in the case of OJ + LPS, rats treated with NAC before LPS (group 5) had lower lipid peroxidation products levels and higher antioxidant products levels as compared to those who did not received NAC (group 4). This phenomenon was not reproducible with NAC administered after LPS (group 6). Thus, results of this study showed that NAC prevents the deleterious effects of LPS in obstructive jaundice by reducing lipid peroxidation in serum and liver/renal tissue if administered before LPS. Nonetheless, NAC failed to prevent the lipid peroxidation in the case of established endotoxemia in obstructive jaundice.     

Intracoronary shunt reduces postoperative troponin leaks: a prospective randomized study.

OBJECTIVE: The purpose of this study was to evaluate whether intracoronary shunt usage reduced the myocardial damage on the basis of the cardiac markers when compared with the shuntless anastomosis in off-pump coronary artery bypass grafting (OPCABG) surgery of isolated left anterior descending artery lesions. METHODS: Forty patients who had stable angina with isolated left anterior descending (LAD) coronary artery lesion undergoing OPCABG surgery were randomized into two groups. Shunt group consisted of 20 patients who had OPCABG using intracoronary shunt, whereas the shuntless group consisted of 20 patients who underwent OPCABG without using intracoronary shunt. Cardiac troponin I, CK, and CK-MB before and 24h after the surgery were assessed in the groups. RESULTS: There were no deaths in the study. The two groups were similar with respect to sex and age. Duration of LIMA-LAD anastomosis was significantly higher in the shunt group (p=0.01). There was no significant difference between the groups concerning the preoperative and postoperative CK and CK-MB levels. The preoperative troponin I levels of the groups were not different (p=0.238; NS), whereas postoperative levels of this marker was significantly higher in the shuntless group (p=0.003). CONCLUSION: Intracoronary shunt reduced the postoperative troponin I levels significantly, so it may be indicated in the patients who are thought to be susceptible to transient ischemia.