A case of dysgraphia induced by sertraline and a review of official spontaneous adverse reaction databases.

WHAT IS KNOWN AND OBJECTIVES: The occurrence of dysgraphia after sertraline intake has never been reported. The objective was to describe a case of this adverse drug reaction and present a review of similar cases held in international databases with a discussion of the possible pharmacological mechanisms. CASE SUMMARY: We observed a 60-year-old man who experienced resting tremors, dyskinesia and dysgraphia 2 months after a stepwise increase in sertraline dosing from 50 to 200 mg/day. WHAT IS NEW AND CONCLUSION: Dysgraphia is a possible adverse drug reaction to sertraline, and we suggest that inhibition of extrapyramidal dopaminergic activity might be the pharmacological mechanism.

Lymphatic edema of the lower limbs after orthopedic surgery: results of a randomized, open-label clinical trial with a new extended-release preparation.

The lymphedema is a high interstitial protein concentration edema, caused by impaired lymphatic transport capacity. It can be primary or secondary. The secondary form may be caused by a lesion of the lymphatic vessels and/or lymph nodes during diagnostic or therapeutic procedures such as surgical interventions. Often, in clinical practice, there is lymphedema after orthopedic surgery, even in minor orthopedic surgery. Lymphedema, typically presents symptoms of swelling, pain, inflammation, and itching, and it can generate, over the years, acute disability in the affected limbs. The standard therapy is mainly represented by medical treatment, such as manual lymphatic drainage and compression with bandages and stockings. In literature it is documented that lymphedema is responsive to alpha and the gamma benzopyrones. The aim of this study was to determine the effectiveness of delayed extended-release formulation of a compound containing apha-benzo-pyrone (Coumarin), benzo-gamma-pyrone (Troxuretina) and oligomeric proanthocyanidins from Vitis vinifera (OPC), in addition to compression therapy, in the reduction of lymphatic edema after prosthetic hip and knee surgery. In the group treated, after 30 days, a reduction was observed of the edema of 4.8% in the ankle area (p less than 0.008) and 2.7% in the calf area (p less than 0.013). The control group showed no significant reduction. The treated group showed a marked reduction of all the secondary symptoms considered in the study, although variations were not significant. The results show that the compound used was effective in reducing edema after major orthopedic surgery, and consequently in alleviating some related symptoms, such as pain, itching, and burning. As an edema has extensive inflammatory components in patients with reduced mobility, the final data seems interesting, however, further investigations and a better follow-up are required.

Throbbing headache associated with enoxaparin administration: a case report, a review of pharmacovigilance databases for similar cases and possible mechanisms.

WHAT IS KNOWN AND OBJECTIVES: To date, no case of headache has been reported with enoxaparin. We present the case of a 60-years-old man, who developed enoxaparin-induced throbbing headache and discuss the possible pharmacological mechanisms. We provide an analysis of enoxaparin-induced headache in three international databases. CASE SUMMARY: A few hours after the subcutaneous administration of this drug at therapeutic dose, the patient experienced throbbing headache. Rechallenge on two other separate occasions separated by several days produced the same effect although with reduced intensity when the dose was lowered. The Naranjo Algorithm indicated a 'certain' relationship. WHAT IS NEW AND CONCLUSION: We report a case of throbbing headache associated with the use of enoxaparin; with the increasing use of enoxaparin, physicians who prescribe this drug should be aware of this potential ADR. We suggest that it is a heparin class-effect, and therefore, a more general caution is also appropriate.

Epidemiological analysis on two decades of hospitalisations for meningitis in the United States.

Bacterial meningitis is an important source of mortality and morbidity worldwide. Data exist on specific vaccines against Streptococcus pneumoniae and Neisseria meningitidis indicating that they reduce the incidence of meningitis, yet comprehensive information on the trend of bacterial meningitis is still lacking. We analysed the Kids' Inpatient Database and the National Inpatient Database considering all bacterial meningitides in the United States, excluding cases of tuberculosis and sexually transmitted diseases. We analysed the trend of meningitis incidence from 1993 to 2011 and in specific age groups before and after the introduction of the pneumococcal conjugate vaccine 7 (PCV-7) and the meningococcal conjugate vaccine 4 (MCV-4). Moreover, we analysed the prevalence of aetiological agents to assess their changes. We estimated 295,706 cases of meningitis having occurred in the United States and a reduction of the discharge rate of 21 %. We observed a significant reduction in cases of meningitis in children and elderly patients following the introduction of the PCV-7. We also found a reduction in subjects aged 10-14 years, an age span consistent with the introduction of MCV-4, although further analyses based on serotypes data are required to confirm this observation. By contrast, we observed an increased prevalence of cases of staphylococcal and streptococcal meningitides. The introduction of PCV-7 has reduced the incidence and changed significantly the aetiology of bacterial meningitis in the United States during the last two decades.

Comparison of intrathecal bupivacaine and ropivacaine with different doses of sufentanil.

BACKGROUND: Spinal bupivacaine produces a complete anaesthetic block of a longer duration than ropivacaine, which leads to a potentially increased risk of failure. A combination of sufentanil to ropivacaine may improve the block's reliability. METHODS: Sixty-four patients, scheduled for varicose vein stripping or the tension-free vaginal tape procedure, were allocated to receive double-blindly, spinal bupivacaine 10 mg (Group 1) or ropivacaine 10 mg without (Group 2) or with sufentanil 2.5 mcg (Group 3), 5 mcg (Group 4). Sensory block was tested with pinprick and motor block was evaluated with the Bromage scale until full recovery. The primary endpoint was to compare the duration of sensory block evaluated by regression to S2. RESULTS: In comparison with bupivacaine, ropivacaine produced a shorter duration sensory block (median at 68, 90 and 120 min in groups 2, 3 and 4, respectively, vs. 150 min in Group 1) and motor block (median at 90, 98 and 120 min in groups 2, 3 and 4 vs. 180 min in Group 1). Motor blockade was significantly less important in patients receiving spinal ropivacaine (median values for the Bromage scale at 3 in groups 2, 3 and 4, vs. 1 in Group 1). Pruritus was significantly more frequent in patients receiving spinal sufentanil (Groups 3 and 4 vs. Groups 1 and 2). CONCLUSION: Plain bupivacaine 10 mg has a longer recovery profile than the same dose of ropivacaine with or without sufentanil.

Surface-induced nonlinearities of liquid crystals driven by an electric field.

We report the study of the effect of a static electric field on the huge optical nonlinearity of methyl-red doped nematic liquid crystals. Experimental data are well fitted using a theoretical model that takes into account the modulation of the surface charge density due to the impinging light beam. It is demonstrated that the optical nonlinearity can be varied by orders of magnitude with application of a low voltage below the threshold of the Fredericks transition. These results confirm the previously proposed model of surface induced nonlinear effects.

Technical solutions for venous outflow reconstruction in damaged liver grafts during procurement: case reports.

The incidence and clinical consequences of hepatic injuries (parenchymal, vascular, and biliary) due to surgical handling during multiorgan procurement are still underestimated. Surgical damage to liver grafts may lead to an increased mortality and graft dysfunction rate; therefore, multiorgan procurements require a high level of expertise and training. We report our experience in two cases of accidental venous outflow damage during liver procurement focusing on our repair strategies. In one case, a short suprahepatic inferior vena cava (IVC) was extended by a venous cuff obtained from a long infrahepatic IVC from the same liver graft. In the second case, we observed a complete transection of the middle hepatic vein during in situ splitting procedure. The damage was reconstructed by cadaveric iliac vein interposition. In both cases, liver transplantation was successfully performed without venous complication. An adequate surgical technique in liver procurement and venous reconstruction during living donor and domino liver transplantation are formidable tools to achieve successful liver transplantation with a damaged graft.

Successful but prolonged resuscitation after local anesthetic-induced cardiac arrest: is clonidine effective?

Local anesthetics when injected intravascularly result in serious cardiac complications including therapy-resistant cardiac arrest. We report a case of cardiac arrest after lumbar plexus block using a combination of 0.5% bupivacaine and 2% lidocaine with epinephrine (1:200.000). Resuscitation was performed by a combination of chest compression, repeated external countershocks and i.v.epinephrine. Clonidine had poor effect. The whole resuscitation required 90 minutes. The patient was discharged four days later without any sequelae. Blood sampling at 10 minutes showed a concentration of 2.02 mg/l lidocaine and 0.87 mg/l bupivacaine. Prolonged resuscitation is necessary in local anesthetic-induced cardiac arrest.

Colossal optical nonlinearity induced by a low frequency external electric field in dye-doped liquid crystals.

We report on the effects of a low-frequency electric field on the optical nonlinear response of thin dye-doped liquid crystal cells. Experimental data show that the external field allows reaching extremely high values of the optical nonlinearity without any critical control of the cell interfaces. A qualitative interpretation of the collected data, based on the light-induced modulation of the bulk voltage through surface modifications, is proposed.

[Occupational therapy in rheumatoid arthritis: short term prospective study in patients treated with anti-TNF-alpha drugs]. / La terapia occupazionale nell'artrite reumatoide: studio prospettico a breve termine in pazienti in trattamento con farmaci anti-TNF-alfa.

OBJECTIVE: To assess the effect of occupational therapy (OT) in rheumatoid arthritis (RA) patients treated with anti-TNF-alpha drugs in a short-term open controlled prospective study. METHODS: 31 RA subjects [(M/F=5/26; mean age= 56 (range=28-73) years; mean disease duration= 165 (range =15-432) months], treated with anti- TNF-alpha drugs, were allocated to OT (n=15) or control (n=16) group. We evaluated at entry and 12 weeks the following outcome parameters including Health Assessment Questionnaire (HAQ), Short-Form Health Survey (SF-36), Global Health (GH), Ritchie index, number of swollen or tender joints, pain, patient and physician disease activity, Disease Activity Score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein CRP) and the correct adherence to items regarding activity daily living (ADL). RESULTS: At baseline, OT and control group had similar demographic and clinical features. After 12 weeks, the changes from baseline of main outcome parameters were not significantly different between the two groups. After 12 weeks, in 7 out of 11 items regarding ADL, the percentage of patients showing a correct adherence was significantly increased in OT group only. Moreover at the end of the study, the OT group showed a correct adherence to 8 out of 11 ADL items in an higher percentage of patients respect to the control group. CONCLUSION: Our study sustains that OT improves self-management but not main parameters of disease activity or functional capacity. Nevertheless educational intervention should be considered as a useful tool in conjunction with pharmacological treatment.

[Norman Bethune (1890-1939), an involved doctor, icon of the blood transfusion history]. / Norman Béthune (1890-1939) médecin engagé et icône de la transfusion sanguine.

Norman Bethune was born in 1890, in Gravenhurst (Ontario, Canada). Thereafter a strong surgical training, he implied in thoracic surgery and fight against tuberculosis. His political opinions led him to join the Republicans in the Spanish Civil War. He played an important part in the development of blood transfusion on the battlefield. Then he joined China with communist troops and therein developed surgical units and accelerated training for health personal. He died of septicemia in 1939.

ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death.

In eukaryotic cells, the nuclear envelope separates the genomic DNA from the cytoplasmic space and regulates protein trafficking between the two compartments. This barrier is only transiently dissolved during mitosis. Here, we found that it also opened at high frequency in migrating mammalian cells during interphase, which allowed nuclear proteins to leak out and cytoplasmic proteins to leak in. This transient opening was caused by nuclear deformation and was rapidly repaired in an ESCRT (endosomal sorting complexes required for transport)-dependent manner. DNA double-strand breaks coincided with nuclear envelope opening events. As a consequence, survival of cells migrating through confining environments depended on efficient nuclear envelope and DNA repair machineries. Nuclear envelope opening in migrating leukocytes could have potentially important consequences for normal and pathological immune responses.

Peripheral analgesic effect of intra-articular clonidine.

Sympathetic nervous system stimulation, which releases noradrenaline, influences the nociceptor activity which develops after tissue injury. The alpha 2-adrenergic agonist, clonidine, produces analgesia through a central mechanism but also inhibits noradrenaline release at terminal nerve fibre endings. Clonidine may induce analgesia when administered at peripheral sites. This study assesses the potential analgesic effect of clonidine after intra-articular administration. Forty ASA I-III patients, scheduled for arthroscopic knee surgery under general anaesthesia were allocated randomly in 4 groups of 10 patients each, at the end of the surgical procedure. In the control group (group 1), the patients received 20 ml of intra-articular isotonic saline. In group 2, the patients received 150 micrograms of clonidine diluted in 20 ml of isotonic saline injected into the knee joint. In group 3, the patients were given 20 ml of intra-articular isotonic saline and clonidine 150 micrograms was injected subcutaneously. In group 4, morphine 1 mg, diluted in 20 ml of isotonic saline, was injected into the knee joint. Postoperative pain was assessed in a double-blind fashion using a visual analogue scale (VAS) at 1, 2, 3, 6 and 24 h after the end of surgery. VAS scores were significantly lower in groups 2 and 4, compared to groups 1 and 3, at 1 and 2 h after surgery. The delay between intra-articular injection and further postoperative analgesic administration was significantly longer (P < 0.05) in group 2 (533 +/- 488 min) compared to groups 1 and 3 (70 +/- 30 min and 132 +/- 90 min, respectively). The difference was not significant between group 4 (300 +/- 419 min) and the other groups. We conclude that a low dose of intra-articular clonidine produces analgesia unrelated to vascular uptake of the drug. This study further supports a peripheral analgesic effect of clonidine.

Localization of the mRNA for the angiotensin II receptor subtype 2 (AT2) in follicular granulosa cells of the rat ovary by nonradioactive in situ hybridization.

The ovary is one of the organs in which an intrinsic renin-angiotensin system (RAS) has been described. Among angiotensin II receptors, the angiotensin II receptor subtype 2 (AT2) is believed to play an important role in mediating or modulating a variety of intraovarian processes. Previous studies were mainly based on ligand binding techniques using AT2 receptor-specific antagonists. Despite the recent cloning of the AT2 gene, no information is available about the exact intraovarian distribution of AT2 mRNA expression. Therefore, we analyzed ovaries from sexually mature, untreated rats by nonradioactive in situ hybridzation using an AT2-specific anti-sense RNA probe. Experiments were performed on perfusion-fixed ovaries obtained from different stages of the estrous cycle. As an important finding, strong AT2 mRNA expression could be demonstrated exclusively in follicular granulosa cells. Follicles containing AT2 mRNA-positve granulosa cells were mainly in the advanced tertiary stage of follicular development, already exhibiting features of atresia. In addition, individual collapsed, definitive atretic follicles also showed strong AT2 mRNA expression solely in granulosa cells. In corpora lutea and in other structures of the ovary, no message for the AT2 receptor could be detected under these conditions. These data may contribute to a better understanding of the effects exerted by an intraovarian RAS. (J Histochem Cytochem 46:865-870, 1998)

Modified par j I allergen from P judaica pollen and its rate of absorption in rats.

Polymerized allergens (allergoids) have been introduced in the immunotherapy of allergic disease in order to reduce the risk of side effects. However, their high molecular weight can be a limit, particularly when they are administered by a route involving passage through the mucosal barrier. We describe a simple procedure aimed at developing an original modified allergen with significantly less allergenic potential (intended as human IgE-binding capacity) but preserving the monomeric nature of the molecule. Par j I, the major allergen of Parietaria judaica pollen, was purified by a combination of monoclonal antibodies and affinity chromatography. Par j I allergen was then modified by reaction with potassium cyanate (KCNO), and compared with the native allergen to evaluate its allergenic potency (RAST-inhibition) and molecular weight (SDS-PAGE). Modified allergen showed significantly lower allergenic potency but kept its original molecular weight, making it particularly suitable for buccal (sublingual) administration. To study the adsorption profile, modified Par j I was radiolabeled and administered intravenously and sublingually to normal rats. The prospects for clinical application of the modified allergen are discussed.

Dot immunobinding assay as a new diagnostic test for human hydatid disease.

Bovine and human hydatid antigens collected from hepatic cysts and characterized by SDS-PAGE immunoblotting show similar patterns. The bovine hydatid antigen has been used to develop a simple and fast in vitro diagnostic assay for human hydatidosis. This method, named HA-DIA (hydatid antigen dot immunobinding assay), consists of incubation of a serum sample with a textile colloidal dye (pink) and a nitrocellulose stick to which the hydatid antigen has been bound. The presence of parasite-specific antibodies leads to dyeing of the stick reactive area, and a coloured spot appears. HA-DIA sensitivity and specificity have been studied in comparison with RAST-IgE and ELISA-IgG by testing 17 sera of patients with hydatid disease and 36 control sera from patients affected with other parasitic and non-parasitic diseases. HA-DIA showed positive results in all the patients' sera and in none of the control sera. Correlation with ELISA--IgG and RAST-IgE was significant. HA-DIA has been demonstrated to be of good predictive value, allowing a speedy diagnosis of hydatid disease. In view of its simplicity, not requiring any laboratory instruments, it is particularly suitable for large-scale field screening.

Additivity of bupivacaine and morphine for peripheral analgesia in rats.

Infiltration of the surgical wound is a classical technique for post-operative analgesia. Recent studies have suggested that local anaesthetic may be combined with other drugs such as opioids. This study has evaluated, in rat, the infiltration with morphine, bupivacaine and their combination. In all groups, the two hind paws were injected with carrageenin. The left hind paw was used as control. The vocalisation threshold to paw pressure (VTPP) of both hind paws was evaluated 2 h after induction of carrageenin inflammation (baseline value), then every 10 min until the return to baseline value after injection of analgesic drugs. The development of oedema was evaluated in both hind paws by measurement of paw circumference (PC) before, then after, carrageenin injection. All analgesic drugs were injected in the right inflamed paw diluted in 0.2 mL of normal saline. The analgesic effect of bupivacaine (0.1, 0.25 and 0.5%), morphine (25, 50 and 100 microg) and their combination (bupivacaine 0.1%/morphine 20 microg, bupivacaine 0.2%/morphine 40 microg and bupivacaine 0.4%/morphine 80 microg) was tested. The effect of naloxone on morphine induced analgesia was tested. The interaction between bupivacaine and morphine was evaluated with an isobolographic analysis. Bupivacaine produced a dose-dependent antinociceptive effect. Morphine infiltration produced a peripheral, dose-dependent analgesic effect antagonised by naloxone. This analgesic effect of morphine was associated with an anti-inflammatory effect. The isobolographic analysis revealed only additivity between bupivacaine and morphine. The infiltration with morphine offers a peripheral analgesic effect which is additive with the effect of bupivacaine. An anti-inflammatory effect of morphine participates in this peripheral analgesic effect.