Hypokalaemia in leukaemia

Five cases are presented which demonstrate the various factors contributing to the development of hypokalaemia and the relevant literature is briefly reviewed. Hypokalaemia is a common finding in leukaemia. Proper evaluation, adequate replacement of potassium and careful follow-up are necessary for prevention of potential dangers related to hypokalaemia.     

In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus

Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment.     

Isolation and functional characterization of a new acidic PLA2 Ba SpII RP4 of the Bothrops alternatus snake venom from Argentina

An acidic protein with phospholipase A₂ activity was purified to homogeneity from the venom of the Northeast Argentinian viperid Bothrops alternatus by two chromatographic steps: a conventional gel filtration on Sephadex G-75 and reversed phase on C18 HPLC column.A molecular mass of 14185.48 Da was determined by mass spectrometry, displaying a homodimer conformation. The kinetic assay demonstrated a catalytically active phospholipase A₂ in correspondence with Asp49 PLA₂ group. The enzyme designated Ba SpII RP4 contains an amino acid composition of 121 residues and a calculated theoretical pI value of 4.88. Amino acid sequence alignments with other Bothrops PLA₂ revealed a high degree of homology sequence (90-56%). Ba SpII RP4 did not show myotoxic activity upon muscular fibers at doses up to 100 μg i.m. route injection or lethal response when it was i.p. injected at the hightest dose of 200 μg. This toxin generates slight biological activities like paw edema inflammation and a delay in the clotting time, although Ba SpII RP4 exhibited catalytic activity. The primary amino acid sequence, determined a quadruple-time of flight (Q-TOF) hybrid mass spectrometer Q-TOF Ultima from Micromass (Manchester, UK) equipped with a nano Zspray source operating in a positive ion mode and tandem mass spectrum, an ESI/MS mass spectrum (TOF MS mode) “de novo amino acid sequencing”, also provides more database about the small group of the non-myotoxic PLA₂s isolated up to the present.     

Renal nerve ablation reduces blood pressure in resistant hypertension: Long‐term clinical outcomes in a single‐center experience

Approximately 10% of patients with hypertension have resistant hypertension, even if adequate pharmacological therapy is established. In this regard, renal nerve ablation (RNA) could represent a valid alternative treatment option. In a retrospective analysis with a follow‐up of 6, 12, and 24 months, the authors investigated the efficacy and safety of catheter‐based renal artery ablation in 57 patients undergoing RNA with multiple renal nerve ablation in both renal arteries. In addition to medical antihypertensive therapy (4.2 ± 1.4 drugs per patient), RNA using three different ablation systems was performed in patients with confirmed resistant hypertension (systolic blood pressure >140 mm Hg in spite of three drugs including a diuretic). The primary end point was the change in office ambulatory systolic blood pressure from baseline to 6, 12, and 24 months of follow‐up after RNA. The primary safety end point was the change in plasma creatinine levels after 12 and 24 months compared with baseline. The mean office systolic blood pressure at baseline was 167.6 ± 22.4 and after 6, 12, and 24 months averaged 143.5 ± 21.1 (P < .05), 141.1 ± 21.1 (P < .05), and 139.4 ± 19.6 mm Hg (P < .05) respectively, with an average of 15.1 ± 5.3 nerve ablations performed. No significant changes in plasma creatinine levels were observed at 12 months (P = .421) and at 24 months (P = .217). There were no complications after RNA nor any relevant adverse vascular, renal, or cardiovascular events observed except in one patient in whom a covered stent had to be placed at the femoral puncture site. In this study, in all patients with resistant hypertension, RNA, if performed adequately in the number of ablations and energy delivery, is an efficient and safe treatment option to lower office and 24‐hour blood pressure. Whether these blood pressure–lowering effects will lead to a reduction of cardiovascular morbidity and mortality will require further studies.     

The role of early radiological studies after gastric bariatric surgery

Background: The authors investigated early radiological findings after gastric surgery for morbid obesity to evaluate their usefulness in avoiding complications or facilitating treatment. Material and Methods: 413 patients underwent gastric bariatric surgery: 327 had vertical banded gastroplasty (VBG), 55 Roux-en-Y gastric bypass (RYGBP), 22 adjustable silicone gastric banding (ASGB), and 9 biliopancreatic diversion (BPD). A radiological upper gastrointestinal investigation employing water-soluble contrast medium was perform ed in each patient between the 2nd and 8th postoperative day. Several techniques were employed to assess different radiological findings related to the anatomic modifications after the bariatric surgery. Results: In VBGs, delayed emptying was found in 10 patients (3%), gastric leak in 3 patients (0.9%), vertical suture breakdown in 1 patient (0.3%), and a wide pouch in 4 patients (1.2%). In RYGBP, a leak was detected in 2 patients (3.6%), delayed emptying in 2 (3.6%), and a wide pouch in 5 (9.1%). ASGB required band enlargement for stomal stenosis in 6 patients (27.2%). Temporary delayed emptying from stomal stenosis was also observed in 2 BPDs (22.2%). Overall complications were 35/413 (8.2%). Two cases of gastric leak after VBG were reoperated. Stomal stenosis after ASGB was treated by percutaneous band deflation; other cases were medically treated until complete healing. Conclusions: Early radiological study after gastric bariatric surgery is advisable, since it detected post operative complications (gastric perforation, stomal stenosis, etc.) and modified the clinical approach. As the interpretation of these radiographs is often difficult, involving different projections or patient's positions or other technical managements, surgeons and radiologists must interact and be knowledgable.     

In vitro and in vivo effects of flubendazole on Echinococcus granulosus metacestodes

The aim of the present work was to determine the efficacy of flubendazole (FLBZ) against Echinococcus granulosus metacestodes by using in vitro and in vivo models. Groups of 50 microcysts developed in vitro, and groups of 10 peritoneal cysts were obtained from Balb C mice with experimental secondary infections of 8 months. The cysts were placed in Leighton tubes containing 10 ml of culture medium. FLBZ was added to the medium resulting in final concentrations of 5 and 1 μg/ml for mycrocysts treatment and 10, 5, and 1 μg/ml for murine cysts treatment. In vivo treatment was performed on 20 mice that developed an experimental secondary hydatid disease over a period of 11 months. FLBZ was given (1.5 mg/kg) by the oral route once a day for 50 days. A loss of turgidity was detected in all in vitro drug treated cysts irrespective of the drug concentration or parasite origin. Inspection of treated cysts by scanning electron microscopy (SEM) revealed that the germinal layer lost it characteristic multicelular structure. These results were confirmed on the ultrastructural level by transmission electron microscopy (TEM), treated metacestodes had undergone considerable degenerative changes after the in vitro treatment. The results obtained after the in vivo treatment with FLBZ showed no significant difference between the control and treated groups related to the weight of cyst masses. However, the ultrastructural study at TEM of cysts that developed in mice from the treated group revealed alterations in the germinal layer with the presence of numerous vacuoles. With regard to the ultrastructural study at SEM, only cellular debris of the germinal layer could be seen. In conclusion, the data obtained clearly demonstrate that in vitro and in vivo treatment with FLBZ is effective against E. granulosus metacestodes.     

Effects of Guar-enriched pasta in the treatment of diabetes and hyperlipidemia

The effect of an alimentary pasta with a 20% (w/w) content of Guar gum was tested in normal volunteers, diabetic and hyperlipidemic patients in different out- and in-patient protocols. Acute experiments (A, B) were carried out in healthy volunteers and in diabetics, by evaluating plasma glucose, triglyceride and insulin changes after a single meal. Plasma glucose and triglyceride rises were almost completely prevented by the pasta in normal volunteers; plasma insulin levels were modified to a lesser extent. In diabetics, the rise of plasma glucose after the meal was significantly delayed. The pasta was also administered for more prolonged periods of time to diabetic and hyperlipidemic patients (experiments C-E). In the first instance, a significant improvement both in the plasma glucose levels, as well as in the daily glucose profile and glycosuria was observed. In hyperlipidemics, a reduction of triglyceride levels was particularly evident; however, in mixed types of hyperlipidemias, a significant hypocholesterolemic effect was also demonstrated. Guar gum pasta may provide a simple dietary addition for the management of common metabolic disorders.     

Multimodal imaging in the differential diagnosis of soft tissue calcinosis

Soft tissue calcinosis is a common radiographic finding, which may be related to different types of pathological processes. Multimodality imaging, combined with analysis of clinical and laboratory data, plays an important role for the differential diagnosis of these conditions. Conventional radiography is considered the first line approach to soft tissue calcinosis; CT and MRI may provide further information to better characterize calcified deposits. Imaging may help to distinguish metabolic calcification, such as primary tumoral calcinosis and the secondary one (associated with acquired disorders of calcium or phosphate regulation), from dystrophic calcification, which is associated to normal blood values of phosphate. The sedimentation sign typical of tumoral calcinosis has been demonstrated by plain film radiography, CT, MRI, and, more recently, by ultrasonography. Other types of soft tissue calcinosis may have a degenerative, metaplastic or neoplastic origin, and their characterization strongly relies on multimodality imaging.     

Development of truncated microtriches inEchinococcus granulosus protoscolices

The development of truncated microtriches in the somatic region of both (a) protoscolices incubated in vitro with two different drugs, i.e. ivermectin or a combination of albendazole and albendazole sulphoxide, and (b) protoscolices removed from hydatid cysts in humans treated with albendazole for 1.5 months is described. Our findings seem to indicate that the development of microtriches is either an indirect effect of treatment with anthelmintics or a possible response to other, as yet unidentified, adverse conditions.