Spinal cord complications of acute schistosomiasis mansoni

5 cases of clinically unsuspected involvement of the spinal cord by S. mansoni are reported. In contrast to the cases usually described in the literature, the nervous system involvement was observed during the acute phase of the infection. One of the patients exhibited a clinical picture closely resembling that of the Guillain-Barré syndrome, and cure was not dependent upon the use of corticoid hormone or antischistosomal therapy. 2 other patients improved after neurological involvement (paraparesis and paraplegia) following the completion of specific treatment (hycanthone). The sudden appearance of a polyradiculoneuritis syndrome was observed in 1 patient during treatment with niridazole. In another patient who developed a sudden transverse myelitis at T.11 with flaccid paraplegia, antischistosomal therapy apparently did not influence the course of the neurological process.It is suggested that the nervous system involvement in the reported cases cannot be explained entirely by the mechanical action of eggs and worms and the resultant granuloma formation. In the authors' opinion an anomalous response of the nervous system to the immuno-allergic products derived from dead worms and; or their eggs probably was responsible for the clinical manifestations of spinal cord involvement.     

Effect of 2-deoxy-D-glucose on Herpetomonas samuelpessoai

Summary The effect of 2-deoxy-D-glucose (2-DG), a carbohydrate analogue, on growth, respiration and fine structure of Herpetomonas samuelpessoai is described.In a glucose-free medium, 2-DG inhibited growth down to 7% that of the control. In presence of equal concentrations of glucose, the inhibition by 2-DG was 55%. With 5 times as much 2-DG as glucose, the inhibition was 88%. Increase in 2-DG in relation to glucose resulted in a progressive inhibition of H. samuelpessoai.Only glucose, fructose or glycerol reversed the inhibition caused by 2-DG in H. samuelpessoai. Glucose was more active than glycerol and fructose. Protection against 2-DG toxicity was confirmed by respirometry experiments. Oxidation of glucose was less affected by 2-DG than that of fructose and glycerol.In presence of 2-DG the cells became round to oval and showed some granules in the cytoplasm. In control cells the mitochondrial cristae were short and straight while in cells treated with 2-DG they were longer and curved. Morphometric analysis of electron micrographs showed that the mitochondrial relative volume of normal cells was 0.084±0.018 while in treated cells were 0.166±0.030.Results are discussed in relation to the carbohydrate metabolism and the mode of action of 2-DG.     

Blink reflex studies in focal dystonias: enhanced excitability of brainstem interneurons in cranial dystonia and spasmodic torticollis

We have studied the orbicularis oculi reflex to paired stimuli in patients with various forms of focal dystonia and in normal controls. In normals, the conditioning stimulus (CS) facilitated the test stimulus (TS) early response (R1), but markedly inhibited the TS polysynaptic late response (R2). In all types of dystonias studied the CS facilitated the TSR1 as in normals. However, in patients with blepharospasm (alone or associated with oromandibular dystonia), spasmodic torticollis, or spasmodic dysphonia, it inhibited the TSR2 significantly less than that of the controls, with marked enhancement of the recovery curve of the late response. The TSR2 recovery curve of patients with focal arm dystonia was normal. These results are indicative of increased brainstem interneuron excitability in the various dystonias mediated by the cranial nerves, but not in focal arm dystonias such as dystonic writer's cramp. This abnormality might be caused by an abnormal input possibly from the basal ganglia upon these brainstem cells. Our results also suggest that a similar pathophysiology underlies the various focal dystonias of the head and neck.     

Gateways to clinical trials

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-chlorotoxin; Ad5CMV-p53, adalimumab, albumin interferon alfa, alemtuzumab, aliskiren fumarate, aminolevulinic acid methyl ester, anakinra, AR-C126532, atomoxetine hydrochloride; Bevacizumab, bosentan, botulinum toxin type B, brimonidine tartrate/timolol maleate; Calcipotriol/betamethasone dipropionate, cangrelor tetrasodium, cetuximab, ciclesonide, cinacalcet hydrochloride, collagen-PVP, Cypher; Darbepoetin alfa, darusentan, dasatinib, denosumab, desloratadine, dexosome vaccine (lung cancer), dexrazoxane, dextromethorphan/quinidine sulfate, duloxetine hydrochloride; ED-71, eel calcitonin, efalizumab, entecavir, etoricoxib; Falciparum merozoite protein-1/AS02A, fenretinide, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gefitinib, ghrelin (human); hLM609; Icatibant acetate, imatinib mesylate, ipsapirone, irofulven; LBH-589, LE-AON, levocetirizine, LY-450139; Malaria vaccine, mapatumumab, motexafin gadolinium, muraglitazar, mycophenolic acid sodium salt; nab-paclitaxel, nelarabine; O6-Benzylguanine, olmesartan medoxomil, orbofiban acetate; Panitumumab, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, peptide YY3-36, pleconaril, prasterone, pregabalin; Ranolazine, rebimastat, recombinant malaria vaccine, rosuvastatin calcium; SQN-400; Taxus, tegaserod maleate, tenofovir disoproxil fumarate, teriparatide, troxacitabine; Valganciclovir hydrochloride, Val-Tyr sardine peptidase, VNP-40101M, vorinostat.     

Are prediction equations for glomerular filtration rate useful for the long-term monitoring of type 2 diabetic patients?

Background. The aim of this study was to compare the accuracyof prediction equations [modification of diet in renal disease(MDRD), simplified MDRD, Cockcroft–Gault (CG), reciprocalof creatinine and creatinine clearance] in a cohort of patientswith type 2 diabetes. Methods. A total of 525 glomerular filtration rates (GFRs) using¹²⁵I-iothalamate were carried out over 10 years in 87 type 2diabetic patients. Accuracy was evaluated at three levels ofrenal function according to the baseline values obtained withthe isotopic method: hyperfiltration (GFR: >140 ml/min/1.73m²; 140 isotopic determinations in 27 patients), normal renalfunction (GFR: 140–90 ml/min/1.73 m²; 294 isotopic determinationsin 47 patients) and chronic kidney disease (CKD) stages 2–3(GFR: 30–89 ml/min/1.73 m²; 87 isotopic determinationsin 13 patients). The annual slope for GFR (change in GFR expressedas ml/min/year) was considered to ascertain the variabilityin the equations compared with the isotopic method during follow-up.Student's t-test was used to determine the existence of significantdifferences between prediction equations and the isotopic method(P < 0.05 with Bonferroni adjusted for five contrast tests). Results. In the subgroup of patients with hyperfiltration, aGFR slope calculated with ¹²⁵I-iothalamate –4.8 ±4.7 ml/min/year was obtained. GFR slope in patients with normalrenal function was –3.0 ± 2.3 ml/min/year. In bothsituations, all equations presented a significant underestimationcompared with the isotopic GFR (P < 0.01; P < 0.05). Inthe subgroup of CKD stages 2–3, the slope for GFR with¹²⁵I-iothalamate was –1.4 ± 1.8 ml/min/year. Thebest prediction equation compared with the isotopic method provedto be MDRD with a slope for GFR of –1.4 ± 1.3 ml/min/year(P: NS) compared with the CG formula –1.0 ± 0.9ml/min/year (P: NS). Creatinine clearance presented the greatestvariability in estimation (P < 0.001). Conclusions. In the normal renal function and hyperfiltrationgroups, none of the prediction equations demonstrated acceptableaccuracy owing to excessive underestimation of renal function.In CKD stages 2–3, with mean serum creatinine 133 µmol/l(1.5 mg/dl), the MDRD equation can be used to estimate GFR duringthe monitoring and follow-up of patients with type 2 diabetesreceiving insulin, anti-diabetic drugs or both.