Direct vs. mediated effects of scorpion venom: an experimental study of the effects of a second challenge with scorpion venom

Objective To assess the respective roles of venom and of catecholamines following scorpion envenomation and to verify whether a second challenge with scorpion venom induces the same consequences than a first one.Design and setting Controlled animal study in a university research laboratory.Subjects Anesthetized and ventilated dogs.Interventions Fifteen dogs received intravenously a sublethal dose of scorpion venom (0.05 mg/kg). In the reenvenomated group (n=5) a second venom challenge with one-half sublethal venom dose was performed 30 min after the first one. The control group (n=10) received saline. Five additional animals served as sham.Measurements and results Plasma toxin and catecholamine levels and a set of usual hemodynamic measurements were repeatedly measured in the first hour following envenomation. In the reenvenomated group another set of measurements was performed 5 min after the second challenge. Changes in toxin, catecholamines, and the main hemodynamic parameters were compared between the study groups. Initial peak toxin levels were similar in the two groups. They induced a striking increase in circulating catecholamines, a fall in heart rate, and an increase in mean arterial and pulmonary artery occluded pressures and in systemic vascular resistance. In the reenvenomated group the second challenge with scorpion venom achieved a toxin blood level similar to the first peak. However, it was not associated with a significant effect either on catecholamines release or on hemodynamics. Subsequent trends in hemodynamic changes were similar to those observed in the control group.Conclusions These data emphasize the limited role of direct effects of scorpion venom on the cardiovascular system and the key role of catecholamines.This research was supported by grants from Secretariat dEtat à la Recherche Scientifique (UR/06/02) and Ministère de la Santé Publique (Tunisia), Institut Français de Coopération (Coopération inter-hospitalière).     

Paracetamol vs piroxicam to relieve pain in renal colic. Results of a randomized controlled trial

Purpose

We tested whether paracetamol could improve pain relief in patients visiting the emergency department with acute renal colic as compared to piroxicam, a nonsteroidal anti-inflammatory drug (NSAID).

Materials and Methods

Patients with a diagnosis of acute renal colic were prospectively randomized to receive either intravenous paracetamol (1 g) or intramuscular piroxicam (20 mg). We monitored patients for visual analog scale (VAS), heart rate, arterial blood pressure, need for rescue therapy, and adverse events at different time points for 90 minutes. We recorded admission requirement and new visit for renal colic at 72 hours. The primary end point was pain relief at 90 minutes, defined as a decrease of 50% or more as compared to the initial VAS. The secondary objectives were comparison of the 2 groups for VAS at any time points and the occurrence of adverse events.

Results

Of the 226 eligible patients, 100 entered the study. Fifty patients received paracetamol and 50 received NSAID. Pain relief at 90 minutes was obtained in 40 patients receiving paracetamol (80%) and 24 (48%) receiving NSAID (P = .002). Visual analog scale was lower in the paracetamol group since 45 minutes. Only 2 adverse events were observed.

Conclusion

A single therapy with intravenous paracetamol more efficiently relieved pain in acute renal colic than did intramuscular piroxicam.     

Pulmonary hypertension in patients with essential thrombocythemia and reactive thrombocytosis

Increased incidence of pulmonary hypertension (PH) has been reported in patients with chronic myeloproliferative disorders. The exact incidence of PH in essential thrombocythemia (ET) is unknown. Most of the reported literature consists of case reports or small studies. We designed this study to asses the incidence of PH in patients with ET and reactive thrombocytosis. Previously or newly diagnosed 46 patients with ET, and 40 patients with reactive thrombocytosis secondary to iron deficiency anemia were found to be eligible for this study. Diagnosis of PH was established via transthoracic echocardiography. PH was found in 22 (47.8%) out of 46 patients with ET. Seven patients with PH were newly diagnosed ET, 5 patients with PH were in low, and the other patients with PH were in intermediate or high risk category. We found statistically significant difference in terms of platelet counts between ET patients with PH and without PH (p = 0.027). None of the patients with reactive thrombocytosis had PH. In conclusion, PH appears to be common in patients with ET. Therefore, all patients with ET should be evaluated for PH. Larger and prospective studies are required to clarify the long-term impact of PH on the survival of these patients. Future studies are also needed to determine whether cytoreductive treatment and aspirin prevent the development of PH, and to determine the effects of cytoreductive treatments and aspirin on the prognosis of PH. The effect of PH on ET prognosis should also be determined in low risk ET patients.     

Unexpected adrenal pheochromocytoma associated with a generalized tonic-clonic seizure in a prepubertal boy: A case report

Rationale:Pheochromocytoma (PHEO) is a rare neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. Most pediatric PHEOs are functional tumors, and clinical manifestations are related to catecholamine hypersecretion and/or tumor mass effects.Patient concerns:We report here a case of a 10-year-old boy with a highly functional adrenal PHEO detected after the evaluation of a generalized tonic-clonic seizure in the patient. His vital signs at admission were: blood pressure up to 220/135 mm Hg; pulse, 112 beats/min; temperature, 37.4°C; respiratory rate, 22 breaths/min.Diagnosis:A 24-hour urine collection for catecholamines test showed a marked increase in Vanillylmandelic acid levels (338.9 μmol/L). An abdominal magnetic resonance imaging revealed a well-defined left adrenal gland mass measuring ∼5 cm in its largest dimension.Interventions:The mass was surgically removed, and histopathological examination revealed PHEO with low malignant potential (Adrenal Gland Scaled Score/PASS/ < 4).Outcomes:The patient was discharged on the 10th postoperative day in good condition. At 24-month follow-up, the patient was doing well without complications such as tumor recurrence, elevated blood pressure, and seizure.Lessons:PHEO should be considered in the differential diagnosis of children with seizures presenting in the emergency department. A multidisciplinary approach to the evaluation and treatment of PHEO is also crucial for a successful outcome.     

Disseminated histiocytoses biomarkers beyond BRAFV600E: frequent expression of PD-L1

The histiocytoses are rare tumors characterized by the primary accumulation and tissue infiltration of histiocytes and dendritic cells. Identification of the activating BRAFV600E mutation in Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) cases provided the basis for the treatment with BRAF and/or MEK inhibitors, but additional treatment options are needed. Twenty-four cases of neoplastic histiocytic diseases [11 extrapulmonary LCH, 4 ECD, 4 extranodal Rosai-Dorfman disease (RDD), 3 follicular dendritic cell sarcoma (FDCS), 1 histiocytic sarcoma (HS) and 1 blastic plasmacytoid dendritic cell neoplasm (BPDCN)] were analyzed using immunohistochemical and mutational analysis in search of biomarkers for targeted therapy. BRAF V600E mutations were detected in 4/11 LCH and 4/4 ECD cases. A pathogenic PTEN gene mutation and loss of PTEN protein expression were identified in the case of HS. Increased expression of PD-L1 (≥2+/≥5%) was seen in 3/4 ECD, 7/8 LCH, 3/3 FDCS and 1/1 HS, with overall 81% concordance between 2 antibodies used in the study (SP142 vs. MAB1561 clone). These results show for the first time significant expression of the PD-L1 immune checkpoint protein in these disorders, which may provide rationale for addition of immune check-point inhibitors in treatment of disseminated and/or refractory histiocytoses.