Diagnostic assessment and therapeutic approach for immunodeficiency due to chylous dysplasia: A case report

Among possible causes of a condition of immunodeficiency, we have to consider the presence of a serious chylous dysplasia, due to the great loss of proteins through the intestinal lumen. A 20‐year‐old male, suffered from diarrhoea (2–4 times a day), weight loss (8 kilos in 5 years), and malnutrition (hypogammaglobulinemia, hypoalbuminemia, leukocytopenia with lymphocytopenia). Accurate diagnostic assessment allowed to diagnose a protein‐losing enteropathy. Conventional oil contrast lymphangiography allowed to accurately assess the case and to establish a proper therapeutic approach. The operation consisted in multiple antigravitational ligatures of dilated and incompetent chylous vessels and chylous vessel‐mesenteric vein microanastomoses. Parameters concerning albumin and leukocytes normalized in 1 week after operation and remained stable with time; there were no more episodes of diarrhoea and the patient recovered weight. An accurate diagnostic assessment and above all lymphangiography allow to diagnose properly difficult cases of immunodeficiency due to intestinal protido‐dispersion and to plan a correct therapeutic functional approach. © 2010 Wiley‐Liss, Inc. Microsurgery 30:401–404, 2010.     

Anesthesia and myotonic dystrophy type 2: a case series

Background

Myotonic dystrophy type 2 (DM2) is a genetically distinct disorder that shares some phenotypical features of myotonic dystrophy type 1 (DM1). However, anesthetic management of patients with DM2 has not been described. The purpose of this study is to report the anesthetic management of a series of patients with DM2 and to describe their response to anesthesia.

Methods

We performed a computerized search of the Mayo Clinic medical records database looking for patients with DM2 who underwent general anesthesia. The medical records were reviewed for anesthetic technique, medications used, and postoperative complications.

Results

We identified 19 patients with DM2 who underwent 39 general anesthetics, 17 monitored anesthetic care cases, and two regional anesthetics. The patients exhibited normal responses to succinylcholine, nondepolarizing neuromuscular blockers, neostigmine, induction agents, and volatile anesthetics. Serious postoperative complications related to DM2 did not occur.

Conclusion

In our series, patients with DM2 tolerated commonly used anesthetics without obvious complications, and they exhibited normal responses to muscle relaxants. These observations suggest that these medications may be used safely in patients with DM2.     

Efficacy of vitamin C vaginal tablets in the treatment of bacterial vaginosis: a randomised, double blind, placebo controlled clinical trial

A randomised, double blind, parallel groups, placebo controlled clinical trial was conducted to assess the efficacy and safety profile of 250 mg ascorbic acid (Vit. C, Vagi C) in women with bacterial vaginosis (BV). Overall, 277 out-patients with at least three of the following signs (white discharge that smoothly coats the vaginal walls, pH of vaginal fluid > 4.5, a fishy odour of vaginal discharge before or after addition of 10% KOH and presence of clue cells on microscopic examination) were randomised to apply a tablet deeply into the vagina once daily for 6 days. The primary efficacy endpoint was the cure rate, defined as the recovery of all inclusion criteria. In the intent-to-treat (ITT) population, cure was achieved by 55.3% of patients with Vit. C (n=141) and by 25.7% of patients with placebo (n=136). The between-group difference was 29.6% (p < 0.001). In the per-protocol (PP) population, cure rate was 66.4% with Vit. C (n=116) and 27.1% with placebo (n = 118), respectively. Between-group difference was 39.3% (p < 0.001). In a subset of patients with centralised evaluation of the vaginal swab, cure in ITT was achieved by 86.3% of patients with Vit. C (n=51) and by 7.6% of patients with placebo (n=53), the between-group difference was 78.7% (p < 0.0001). Cure rate in PP was 86.0% with Vit. C (n=50) and 6.1% with placebo (n=49), between-group difference was 79.9% (p < 0.0001). Both Vit. C and placebo were well tolerated and no differences in safety profile were evident between groups. The results support an effective and safe use of silicon-coated Vit. C vaginal tablets in the management of BV.     

Non-nucleoside inhibitors of human adenosine kinase: synthesis, molecular modeling, and biological studies

Adenosine kinase (AK) catalyzes the phosphorylation of adenosine (Ado) to AMP by means of a kinetic mechanism in which the two substrates Ado and ATP bind the enzyme in a binary and/or ternary complex, with distinct protein conformations. Most of the described inhibitors have Ado-like structural motifs and are nonselective, and some of them (e.g., the tubercidine-like ligands) are characterized by a toxic profile. We have cloned and expressed human AK (hAK) and searched for novel non-substrate-like inhibitors. Our efforts to widen the structural diversity of AK inhibitors led to the identification of novel non-nucleoside, noncompetitive allosteric modulators characterized by a unique molecular scaffold. Among the pyrrolobenzoxa(thia)zepinones (4a-qq) developed, 4a was identified as a non-nucleoside prototype hAK inhibitor. 4a has proapoptotic efficacy, slight inhibition of short-term RNA synthesis, and cytostatic activity on tumor cell lines while showing low cytotoxicity and no significant adverse effects on short-term DNA synthesis in cells.     

Synthesis and antiplasmodial activity of bicyclic dioxanes as simplified dihydroplakortin analogues

Here we report the synthesis and evaluation of antiplasmodial activity of a novel series of bicyclic peroxides inspired by the marine natural compound dihydroplakortin. We developed a synthetic strategy leading to the dihydroplakortin-related peroxides in only a few steps. The in vitro antiplasmodial potency of the peroxides was similar to, or greater than, that of the reference natural compound, and structure-activity relationship studies revealed several key structural requirements for activity and potency.     

CEA increase as a marker of disease progression after first-line induction therapy in metastatic colorectal cancer patients. A pooled analysis of TRIBE and TRIBE2 studies

Background In mCRC, CEA is used to monitor response to systemic therapy together with imaging. After the end of induction, no major improvement in tumour shrinkage is expected, and the availability of a marker able to predict progressive disease (PD) versus no-PD might allow avoiding CT scans.Methods We pooled data from patients with baseline CEA ≥ 10 ng/mL included in TRIBE and TRIBE2 studies with the aim of identifying a threshold for percent increase of CEA from nadir able to predict PD after the end of the induction therapy.Results In total, 1178 paired CEA and radiological assessments from 434 patients were included. According to the optimal cut-off determined by ROC, a CEA increase of at least 120% from nadir differentiated between PD and no-PD with a sensitivity of 74% and a specificity of 78%, excluding PD in the 92% of radiological assessments and allowing to avoid the 67% of CT scans. However, CEA cut-off of 120% was not able to detect radiological PD in 26% of cases. In order to mitigate this issue, a different clinically relevant threshold was evaluated based on the best sensitivity cut-off. Therefore, using any CEA increase from nadir as a threshold, the sensitivity grew to 93% and only in the 7% of cases the radiological PD was not detected.Conclusions In mCRC with baseline CEA ≥ 10 ng/mL, CEA values can accurately predict PD versus no-PD after the end of the first-line induction therapy.Subject terms: Predictive markers, Colorectal cancer     

Myelofibrosis: Prognostication and cytoreductive treatment

Myeloproliferative neoplasms include three diseases: polycythemia vera, essential thrombocythemia and primary myelofibrosis (PMF), currently diagnosed according to the 2008 World Health Organization criteria. Patients with PMF may encounter many complications, and, among these, disease progression is the most severe. Concerning prognostication of Myelofibrosis (MF), the International Prognostic scoring system (IPSS) (International Prognostic Scoring System) model at diagnosis and the Dynamic IPSS (DIPSS) anytime during the course of the disease may be useful to define survival of MF patients. The IPSS and the DIPSS are based on age greater than 65 years, presence of constitutional symptoms, hemoglobin level less than 10 g/dL, leukocyte count greater than 25 × 10⁹/L, and circulating blast cells 1% or greater. Cytogenetic profile and mutational analysis seem to be the next step to implement MF prognostication. Concerning treatments, hydroxyurea has been considered until now the drug of choice when an anti-myeloproliferative effect is needed, but recent data on JAK inhibitors demonstrated a significant effect of these drugs on splenomegaly and symptoms.     

Comparative Study of Various Immune Parameters in Three Bivalve Species during a Natural Bloom of Dinophysis acuminata in Santa Catarina Island, Brazil

This study aimed to verify if Dinophysis acuminata natural blooms affected the immune system of three bivalves: the oyster, Crassostrea gigas, the mussel, Perna perna, and the clam, Anomalocardia brasiliana. Animals were obtained from a renowned mariculture farm in the southern bay of Santa Catarina Island during, and 30 days after (controls), an algal bloom. Various immunological parameters were assessed in the hemolymph of the animals: total and differential hemocyte counts, percentage of apoptotic hemocytes, protein concentration, hemagglutinating titer and phenoloxidase activity. The results showed that the mussel was the most affected species, with several altered immune parameters, whereas the immunological profile of clams and oysters was partially and completely unaffected, respectively.     

Autonomic nervous system instability, tetanic necrosis of the heart and myocardial TNFalpha expression in a tetanus fatal case

The cardiovascular manifestations of tetanus consist of disturbances of heart rate and rhythm, blood pressure instability, arrhythmias, myocardial dysfunction and sympathetic overactivity. It was suggested that either a sudden loss of catecholamine stimulation or myocardial damage caused by the direct action of the tetanus toxin, could be involved in cardiac dysfunction described in tetanus. However, histologic evidence of myocardial necrosis in tetanus was demonstrated in few cases. We report a fatal case of tetanus in which we investigated the cardiac morphology and the expression of TNFalpha to elucidate the heart involvement in this case. Since it is well known that myocardial damage caused by catecholamines can induce synthesis of cytokines by myocytes, cytokines, specifically those with known cardiodepressant properties such as TNF-alpha, could be an alternative mechanism involved in cardiac dysfunction in the setting of tetanus.