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.     

Congestive gastropathy

15 patients with congestive gastropathy were reported including clinical and pathological characteristics of the disease. Every patient had alcoholic liver cirrhosis and portal hypertension. 6 patient's stomach was resected while in 2 further cases the disease was found at autopsy. In additional 7 cases the characteristic microvascular changes were observed in endoscopic biopsy specimens from the gastric mucosa. The authors presume that this disease has an acute and a chronic stage. In the acute stage dilated capillaries are present under the surface, not related to the inflammation of gastric mucosa. This phenomenon was described in the literature. In the chronic stage there are dilated and tortuous vessels in the submucosal layer surrounded by collagenous connective tissue. The authors suppose that the thick and fibrotic submucosal layer causes microcirculatory disturbances in the gastric mucosa. The impaired microcirculation may cause extensive ulcers with profuse and sometimes lethal bleeding.     

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.     

Isolated leukemic iritis in childhood

Case report on a child with acute lymphogenous leukemia. Although there was constant hematological remission she developed an isolated leukemic iritis and secondary glaucoma. The clinical picture showed a characteristic stratification of the hyphema. After the patient had remained seated for a prolonged period of time the leukemic cells settled above the erythrocytes, forming a so-called pseudohypopyon, which diagnostically important. Cytologic examination after anterior chamber paracentesis is indispensable in order to establish the etiology of the disease. Isolated leukemic iritis may be the first sign of a relapse and therefore indicate a need to reinstitute induction therapy.     

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.     

The relationship between anti-human eye muscle antibodies and thyroid function, anti-TSH receptor antibodies and eye symptoms in Graves' ophthalmopathy.

Circulating IgG, IgA, and IgM antibodies to human eye muscle cytosol antigens were studied in 60 patients with Graves' ophthalmopathy using the indirect ELISA method. There was a significant difference in the levels of both IgG and IgA antibodies between the patients with Graves' ophthalmopathy and a control group (p < 0.001). IgA antibodies to eye muscle cytosol antigens were raised in 20 out of 29 patients with proptosis (class 3 ophthalmopathy), in comparison with 31 patients out of the total group of 60 with Graves' ophthalmopathy (p < 0.02). Anti-TSH receptor antibodies (TRAK) were not present in over half of the 31 patients with raised IgA antibodies to eye muscle antigens. However, a significant difference was found between the levels of IgG and IgA antibodies in the TRAK-negative patients (p < 0.05). These findings suggests that both IgG and IgA antibodies to eye muscle antigens might be important in the development of ophthalmopathy.