Human Calcitonin Delivery in Rats by Iontophoresis

Abstract— In-vitro iontophoresis (0·33 mA cm⁻²) of calcitonin (50 μg mL⁻¹, pH 4) was performed with the hairless rat skin model. Direct current was as potent as pulse current (2·5 kHz on/off 1/1) iontophoresis in promoting transdermal permeation of calcitonin. Increase in duration of current application from 20 min to 1 h did not increase calcitonin flux. Results suggest that calcitonin can be blocked in the skin pores through which it travels or can accumulate in the skin and be progressively released from the depot. Invivo experiments showed that transdermal iontophoretic administration of calcitonin induced a hypocalcaemic effect in rats.     

Radiofrequency Catheter Ablation of Atrial Flutter Induces the Release of Platelet and Leukocyte-Derived Procoagulant Microparticles and a Prothrombotic State

Background: To assess the extent of endothelium, platelet, and leukocyte damage and coagulation activation induced by radiofrequency catheter ablation (RF) of atrial flutter. In the vasculature, procoagulant microparticles (MPs) are reliable markers of vascular damage. They provide an additional phospholipidic surface, enabling the assembly of the enzyme complexes of blood coagulation and consequent thrombin generation.
Methods: MPs were measured in the venous blood of 33 patients with isthmus-dependent atrial flutter undergoing RF before (RF₀), immediately after (RF₁), and at day 1 (RF₂) thereafter. Concentrations of PAI-1, vWF, and D-dimers were simultaneously determined. MPs procoagulant activities were determined using a functional prothrombinase assay. RF induces an early rise of platelet-derived MPs (platelet), vWF Ag, and D-dimers levels, which is concomitant with the decrease of PAI-1 concentrations. Conversely, no significant changes in endothelial-derived MPs could be evidenced. At RF₂, sustained elevation of leukocytes-derived MPs, vWF, and D-dimers testified to an ongoing prothrombotic status.
Conclusion: RF ablation of common flutter induces a prothrombotic state and the release of platelet and leukocyte-derived procoagulant microparticles. Whereas this activation of blood coagulation could be viewed as clinically marginal in right-sided procedures, its relevance in left-sided procedures should be established.     

Cholesterol lowering therapy inhibits the low-flow mediated vasoconstriction of the brachial artery in hypercholesterolaemic subjects

1 We tested whether lipid lowering treatment with HMG CoA reductase inhibitor modified the flow mediated large artery reactivity in primary pure hypercholesterolaemia.
2 Abnormalities in arterial reactivity have been described in the presence of high blood cholesterol, in particular an enhanced constriction of the brachial artery in response to acute induction of a low flow state.
3 Using pulsed-Doppler, we measured brachial artery diameter and flow velocity at rest and their changes induced by wrist occlusion before and after 3 months of double-blind treatment by pravastatin (40  mg orally) in 13 subjects and placebo in 15 others.
4 The significant decrease ( P <0.01) in diameter induced by wrist occlusion before (0.34±0.08  mm) placebo and pravastatin (0.39±0.10  mm) persisted after placebo (0.26±0.07  mm) but was abolished after pravastatin (0.07±0.05  mm). The absolute change in diameter induced by wrist occlusion was lower after than before pravastatin ( P <0.01) and lower after pravastin than after placebo ( P <0.05). Diameter during wrist occlusion was higher after pravastatin than after placebo (4.35±0.16 vs 3.89±0.09  mm); P <0.01).
5 These findings indicate that the lipid changes induced by pravastatin and/or some unknown but direct mechanism of the drug itself inhibit low-flow-mediated vasoconstriction associated with hypercholesterolaemia. Such effects may have important implications for the treatment of vasospasm often seen in the presence of high blood cholesterol.     

A study of the gross motor skills of cerebral palsied children in an adventure playground for handicapped children

SUMMARY The research study involved a comparison of the range of physical abilities elicited by clinical assessment, with motor behaviour in the ploys ground.     

STABILITY OF FREE AND TOTAL PROSTATE SPECIFIC ANTIGEN IN SERUM FROM PATIENTS WITH PROSTATE CARCINOMA AND BENIGN HYPERPLASIA

Purpose

Instability of prostate specific antigen (PSA) in serum might complicate the interpretation of the free-to-total PSA ratio. We studied the in vitro stability of free PSA and total PSA in serum of patients with prostate cancer or benign prostate hyperplasia (BPH), and of elderly man without known prostate disease. Furthermore, we investigated conditions to stabilize the in vitro values in serum.

Materials and Methods

The effects of storage at 4C on free and total PSA were investigated in serum of 32 men with prostate cancer, 25 with BPH and 29 older than 70 years. All had total PSA less than 25 micro g./l. The influence of total PSA levels on in vitro changes in free-total PSA was studied in serum of 39 other prostate cancer patients (total PSA 1.7 to 298 micro g./l.). Stabilization studies were performed in yet another series of samples from 54 prostate cancer patients (total PSA 1.3 to 238 micro g./l.) by adjustment of serum pH to 5.5 before storage. Free and total PSA was measured by a commercial immunofluorometric assay, as well as by in-house immunofluorometric assays. Statistical analyses of the results were performed by analysis of variance with repeated measures.

Results

We found no difference between the results obtained by the 2 assay systems. After 7 days at 4C there was a slight decrease in total PSA in sera of prostate cancer patients, BPH patients and men older than 70 years. A decrease in mean free PSA values occurred in all groups (21.3, 15.7 and 14.6%, respectively). The decrease of free PSA with time was significant (p <0.0001) in all groups but there was no significant difference among the groups (p = 0.16). The concomitant decrease in free-to-total PSA ratio was significant in all groups (p <0.0001). This change was group dependent (p = 0.003), with the largest decrease in the prostate cancer group. Large interindividual differences were observed. Storage at 4C for 7 days of sera of 39 patients with localized and disseminated prostate cancer (total PSA 1.7 to 298 micro g./l.) gave a more pronounced decrease in free PSA than in total PSA. Adjustment of serum pH to 5.5 had a stabilizing effect on free PSA and on the free-to-total PSA ratio, giving a significantly smaller change in both values (p <0.0001).

Conclusions

In vitro instability of free PSA in serum and large interindividual differences should be considered when using the ratio of free-to-total PSA in evaluation of patients with suspected prostate cancer. Serum samples should be stored frozen if not analyzed immediately or acidified to pH 5.5. Interpretation of data from determination of free-to-total PSA ratio should be done with caution if the sampling and storage conditions are not known.     

Sevoflurane for central catheter placement in neonatal intensive care: a randomized trial

Objective: To compare the efficacy and safety of sevoflurane deep sedation with glucose and nonnutritive sucking (GNNS) in reducing the duration of the procedure and in preventing pain‐related effects during peripherally inserted central catheter (PICC) placement. Background: PICC placement in neonatal intensive care is a delicate and stressful procedure that requires pain prevention. GNNS has been recommended in this situation but remain often inefficient. Methods: We designed a randomized controlled study in a sixteen‐bed pediatric and neonatal unit in a tertiary hospital. Fifty‐nine neonates at >28 weeks of gestation with continuous positive airway pressure or invasive mechanical ventilation and requiring PICC placement were included. Patients were randomized to receive inhaled sevoflurane (IS) or glucose and non‐nutritive sucking (GNNS). Procedural duration and conditions, hemodynamic and respiratory parameters, occurrence of movements and complications were compared ( http://clinicaltrials.gov trial register no. NCT00420693). Results: The two groups had similar demographics. There were no between‐group differences in procedural duration (P = 0.84) despite greater immobility in IS group (P = 0.017). IS was also associated with fewer episodes of hypertension (P = 0.003), tachycardia (P < 0.001), and bradycardia (P = 0.02). Occurrences of hypotension were not different between the groups (P = 0.06). The GNNS group showed more desaturation during the 4 h after the procedure (P = 0.03). Complications during intensive care stay did not differ between groups. Conclusion: Inhaled sevoflurane does not make easier catheters placement but prevent pain‐related symptoms. Because sevoflurane is responsible for hypotension, it requires careful monitoring and treatment adaptation.     

Obsessive Compulsive Disorder in a Patient with Twiddler's Syndrome

Twiddler's or twist syndrome is the twisting of pulse generators around themselves. It may result from mechanical manipulation that can induce the malfunction of the device. In this case, twiddler's syndrome resulted from compulsive checking of the device. The implantable cardioverter‐defibrillator (ICD) triggered the development of an obsessive compulsive disorder (OCD). Two invasive procedures were required to replace the ICD. Psychiatric intervention prevented the recurrence of twiddler's syndrome in this patient for more than 2 years. We believe that preimplant psychiatric assessment should be the rule.     

Early head growth: relation with IQ at 8 years and determinants in term infants of low and appropriate birthweight

Aim  To investigate the relation between head growth at different periods and IQ at 8 years, and to identify factors associated with more rapid head growth.
Method  Two parallel cohorts of term low birthweight (LBW) and appropriate birthweight (ABW) infants were enrolled at birth in northeast Brazil. Anthropometric measurements were made at birth, 2 months, 6 months, 12 months, 24 months, and 8 years. Cognition was assessed at 8 years ( n =164) with the Wechsler Intelligence Scale for Children. Multivariable analysis with a two-stage residual model was used to relate head growth between successive time points with IQ.
Results  Mean birthweight was 2.35kg (SD 0.15) in the LBW group (33 males, 50 females), and 3.21kg (SD 0.15) in the ABW group (28 males, 53 females). Mean gestational age was 38.8 weeks (SD 1.4) and 40.0 weeks (SD 1.3) respectively. In the LBW group, head growth from birth to 2 months and from 2 to 6 months, conditional on previous size, were significant independent predictors of IQ at 8 years. Conditional head growth from 6 months to 8 years and head size at birth were unrelated to IQ. In the ABW group there was no significant relation between conditional head growth and IQ for any period. Determinants of more rapid head growth from birth to 6 months in LBW infants were maternal height and rate of infant weight gain.
Interpretation  Head growth from birth to 6 months in term LBW infants is more important than prenatal or later postnatal head growth in predicting IQ at 8 years.     

Complicated Forms of Tachycardia‐Mediated Cardiomyopathy Associated with Idiopathic Left Ventricular Tachycardia

Idiopathic left ventricular tachycardia is an infrequent form of ventricular tachycardia associated with a structurally normal heart. The prognosis is usually benign; however, sustained cases have been reported. In this report, we describe two cases of persistent idiopathic left ventricular tachycardia complicated by tachycardia‐mediated cardiomyopathy. In the first case, the patient developed a right ventricular thrombus with subsequent pulmonary embolism. In the second case, the patient developed acute pulmonary edema. Both cases were cured by catheter ablation. (PACE 2011; e52–e55)