Efficacy and safety of a T-type calcium channel blocker in patients with neuropathic pain: A proof-of-concept, randomized, double-blind and controlled trial.

BACKGROUND: T-type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (ETX), an anticonvulsant and a T-type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain. METHODS: This proof-of-concept, multicentre, double-blind, controlled and randomized trial compared the efficacy and safety of ETX (given as add-on therapy) to an inactive control (IC) in 114 patients with non-diabetic peripheral neuropathic pain. After a 7-day run-in period, eligible patients aged over 18 years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention-to-treat population. This study is registered with EudraCT (2013-004801-26) and ClinicalTrials.gov (NCT02100046). RESULTS: The study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. ETX failed to reduce total pain and showed a poor tolerance in comparison to IC. In the per-protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI -25.8; -5.4) from baseline compared to IC (-7.8%, 95% CI -14.3; -1.3; p = 0.033), but this result must be interpreted with caution because of a small subgroup of patients. CONCLUSION: Ethosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events. SIGNIFICANCE: This article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per-protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T-type calcium channel inhibition for the treatment of neuropathic pain.

Complication-related removal of totally implantable venous access port systems: Does the interval between placement and first use and the neutropenia-inducing potential of chemotherapy regimens influence their incidence? A four-year prospective study of 4045 patients.

BACKGROUND: Totally implantable venous access port systems are widely used in oncology, with frequent complications that sometimes necessitate device removal. The aim of this study is to investigate the impact of the time interval between port placement and initiation of chemotherapy and the neutropenia-inducing potential of the chemotherapy administered upon complication-related port removal. PATIENTS AND METHODS: Between January 2010 and December 2013, 4045 consecutive patients were included in this observational, single-center prospective study. The chemotherapy regimens were classified as having a low (<10%), intermediate (10-20%), or high (>20%) risk for inducing neutropenia. RESULTS: The overall removal rate due to complications was 7.2%. Among them, port-related infection (2.5%) and port expulsion (1%) were the most frequent. The interval between port insertion and its first use was shown to be a predictive factor for complication-related removal rates. A cut-off of 6 days was statistically significant (p = 0.008), as the removal rate for complications was 9.4% when this interval was 0-5 days and 5.7% when it was ≥6 days. Another factor associated with port complication rate was the neutropenia-inducing potential of the chemotherapy regimens used, with removal for complications involved in 5.5% of low-risk regimens versus 9.4% for the intermediate- and high-risk regimens (p = 0.003). CONCLUSION: An interval of 6 days between placement and first use of the port reduces the removal rate from complications. The intermediate- and high-risk for neutropenia chemotherapy regimens are related to higher port removal rates from complications than low-risk regimens.

[Retrospective study of neuromeningeal cryptococcosis in patients infected with HIV in the infectious diseases unit of university hospital of Casablanca, Morocco]. / Étude rétrospective de la cryptococcose neuroméningée chez les patients infectés par le VIH dans le service des maladies infectieuses du CHU de Casablanca, Maroc.

OBJECTIVE: To report the cases of neuromeningeal cryptococcosis and to describe the clinical, paraclinical, therapeutic and outcomes of patients. PATIENTS AND METHODS: Retrospective study of 43 patients infected with HIV admitted from January first 2010 to June 30th 2015 in the infectious disease unit of UHC Ibn Rochd, for neuromeningeal cryptococcus. RESULTS: The mean frequency of neuromeningeal cryptococcosis in patients infected with HIV was 1.4%. The mean age was 39 years and a sex ratio of 1.38. The mean CD4 count was 70 cells/mm3. The diagnosis of HIV was revealed by neuromeningeal cryptococcus in 77% of cases. Fifteen days interval was reported between the first symptom and hospital admission. Headache (77%) was the most represented clinical sign. The cerebrospinal fluid analysis showed hypoglycorachy (67%), hyperproteinorachy (65%) and lymphocytosis (63%). Chinese ink direct examination for Cryptococcus neoformans in CSF was positive in 86% of cases and all cases were positive after culture on Sabouraud's medium. Patients were treated with monotherapy amphotericin B (42%) or fluconazole (28%) and bitherapy amphotéricine B/fluconazole (28%). Fatal evolution was observed in 60% of cases. CONCLUSION: Neuromeningeal cryptococcosis remains a severe opportunistic infection in HIV patients with a heavy mortality rate.

Prognostic significance of cyclooxygenase-2, epidermal growth factor receptor 1, and microvascular density in gastric cancer.

Gastric cancer remains a significant global health burden with poor treatment outcome. New treatment modalities that target inflammation, proliferation, and angiogenesis have been used in various cancers, including gastric cancer. We sought to study the pattern of expression of two important proteins, cyclooxygenase-2 and epidermal growth factor receptor, and their association with microvascular density, clinicopathological features, and survival in Arab Omani patients with gastric cancer. Formalin-fixed, paraffin-embedded tumors were studied by immunohistochemistry using monoclonal antibodies to cyclooxygenase-2, epidermal growth factor receptor, and CD34. The immunohistochemical results were correlated with clinicopathological features and survival. In our study population, we found a male/female ratio of 72:43, a median age of 59 years, stage III and IV incidence of 66.9%, and a median follow-up of 96 months. Positive expression rates of cyclooxygenase-2 and epidermal growth factor receptor were 89.6 and 23.5%, respectively. The median microvascular density value was 52.5. When this value was determined as the cut-off point, 50% of patients were found to have high microvascular density. Epidermal growth factor receptor over-expression correlated with high microvascular density values, advanced lymph node involvement (N3), and TNM stage presentation (III and IV). Similarly, lymph node involvement was associated with cyclooxygenase-2 over-expression and high microvascular density. Univariate analysis showed that epidermal growth factor receptor over-expression, pathological T3 and T4 disease, and overall stage III and IV disease were adverse prognostic factors. On multivariate analysis using a Cox regression model, expression of epidermal growth factor receptor, and advanced TNM stage were significant adverse prognostic factors for overall survival. Expression of epidermal growth factor receptor in Arab Omani patients with gastric cancer correlates with aggressive tumor characteristics and is an independent prognostic factor. Further clinical studies are needed to evaluate the utility of epidermal growth factor receptor immunohistochemistry as a tool for gastric cancer treatment.

Totally implantable venous access port systems and risk factors for complications: a one-year prospective study in a cancer centre.

BACKGROUND: Totally Implantable Venous Access Port Systems (TIVAPS) are widely used in oncology, but complications are frequent, sometimes necessitating device removal and consequently delays in chemotherapy. The aim of this study was to investigate possible risk factors for morbidity. METHODS: A total of 815 consecutive cancer patients (median age: 56.2 years [0.8-85.2]; 522 female) were enrolled in this observational, single-centre study between May 2nd 2006 and April 30th 2007. TIVAPS implantation involved principally cephalic or external jugular vein access. Patients were followed up for one year unless the device was removed earlier. RESULTS: The overall morbidity rate was 16.1% (131/815). Complications necessitated device removal in 55 patients a mean of 3.7 months [0.2-12.0] after implantation. These comprised TIVAPS-related infection (19), port expulsion (14), catheter migration (6), venous thrombosis (5), mechanical problems (3), skin disorders (2), pain (2), drug extravasation (2) infection unrelated to TIVAPS (1) and inflammation (1). No patient died during the study. The factor most strongly predictive of complications was the interval between insertion and first use of the TIVAPS, ranging from 0 to 135 days (median: 8.0 days). The morbidity rate was 24.4% when this interval was 0-3 days, 17.1% when it was 4-7 days and 12.1% when it exceeded 7 days (p < 0.01; Chi(2) test). The median interval was 6 days (0-53) and 8 days (0-135), respectively, in patients with and without complications (p < 0.001). CONCLUSION: To reduce complications, an interval of at least 8 days between placement of the TIVAPS and its first use may be advisable.

Experimental xylazine-ketamine anesthesia in the common carp (Cyprinus carpio).

The potential anesthetic effect of ketamine in combination with xylazine was examined in the common carp (Cyprinus carpio). Anesthesia (indicated by cessation of voluntary swimming and loss of responses to pinching the skin with forceps and pricking the tail with a needle) was induced by mixing 14.4 ml of ketamine (5% solution), or 11.4 ml of xylazine (2% solution), or both, in 10 l of water containing 10 fish/group. Xylazine alone induced sedation and anesthesia in 5-12.3 min with a mean duration of 7.3 min. Ketamine alone induced similar effects in 7.2-9.7 min for an average of 24.2 min. Combined xylazine and ketamine took longer (14-22.8 min) to induce sedation and anesthesia, but the duration was longer (42.7 min). The respiratory rates of anesthetized fish significantly decreased in all treatments when compared to controls. In conclusion, the combination of xylazine-ketamine was found to induce smooth anesthesia in the common carp for a time sufficient for common clinical and surgical interventions.

Cotyledonoid leiomyoma in pregnancy.

BACKGROUND: Benign smooth-muscle tumors (leiomyomata) are the most frequent tumors found in the female genital tract. They are easy to diagnose in pregnancy and usually managed conservatively. Some variant forms with unusual infiltrative growth pattern have been known, but they are rare in pregnancy. The variant forms pose diagnostic and management difficulties. CASE: An unusual type of leiomyoma (cotyledonoid), adhering to the bowels and occupying the whole left broad ligament, was excised completely at 14 weeks of gestation, and the pregnancy continued to term. CONCLUSION: Familiarity with benign uterine smooth-muscle tumors with unusual growth patterns by gynecologists and pathologists is essential in avoiding over-treatment.

Regional genetic differentiation of Phlebotomus sergenti in three Moroccan foci of cutaneous leishmaniasis caused by Leishmania tropica.

Phlebotomus sergenti was identified morphologically in samples from three Moroccan foci of leishmaniasis caused by Leishmania tropica in the provinces of Azilal, Essaouira and Taza. Three primary mitochondrial DNA lineages were identified, and they could be markers for regionally distributed cryptic species. Greater mitochondrial diversity in Azilal indicated that this central province could have been the origin of dispersal of P. sergenti or the zone of secondary contact. All except one of the 21 mitochondrial haplotypes showed a marked regional distribution, and this indicates that vector control would not always be followed by rapid, long-distance reinvasion. Only mitochondrial haplotype SER18 was a putative marker for long-distance dispersal, for which there is no evidence of human assistance.

Congenital lumbar hernia in association with carpus equina varus.

A rare case of congenital lumbar hernia associated with carpus equina varus is described in a week old baby. The treatment is described with limited review of the literature.

Coumarins from Cedrelopsis grevei (Ptaeroxylaceae).

The stem bark of Cedrelopsis grevei Baill. has yielded the first reported examples of 5-prenylated coumarins, cedrecoumarin A and B as well as the known coumarins, cedrelopsin, scoparone, O-methylcedrelopsin and norbraylin, and the known chromones ptaeroglycol and ptaeroxylinol.

[Leishmania tropica cutaneous leishmaniasis in an emerging focus in North Morocco: new clinical forms]. / Leishmaniose cutanée à Leishmania tropica dans un foyer émergent au nord du Maroc: nouvelles formes cliniques.

INTRODUCTION: Leishmania tropica cutaneous leishmaniasis is usually described as dry, small and self-healing lesions, mainly located on the face and occurring in stable endemic foci. In 1989, similar aspects were observed in a rural hypoendemic focus in center Morocco where about 60 cases were diagnosed. In contrast, an epidemic urban focus in Taza-North Morocco--was identified in 1995 with peculiar clinical aspects. Our objectives is to describe these clinical characteristics. PATIENTS AND METHODS: From October 1995 to November 1996, 132 cases were diagnosed from this new focus during a monthly active survey. Age, sex, duration of lesions, clinical aspects and therapeutic regimen were detailed for each patient. RESULTS: Among the patients, 56.8 p. 100 were women. Mean age was 24.6 +/- 21.5 years (range: 8 months to 85 years). The mean duration of lesions was 6.9 +/- 6.5 months and 91.4 p. 100 evoluted for less than one year. Impetiginized, ulcerocrusted and noduloulcerative forms were predominant (61 p. 100). Furthermore, severe, vegetant inflammatory and multiple lesions were observed in infants and elderly patients. Limbs were involved in 30 p. 100 of cases. Eighty-six patients were treated with intralesional glucantime regimen and cured in 72 p. 100 of cases. Intramuscular treatment by glucantime was required in case of multiple lesions and failure of local therapy. DISCUSSION: In this study, the high frequency of severe lesions in infants and elderly patients suggests that the introduction of the parasite occurred recently in this area. The brief duration of lesions confirms the acute character for cutaneous leishmaniasis related to L. tropica in this epidemic focus. The host immune status associated with parasite intrinsic factors probably plays a role in these perculiar clinical manifestations.

[Gastrointestinal myiasis. Apropos of 1 Moroccan case]. / La myiase gastro-intestinale. A propos d'une observation marocaine.

This observation relates an exceptional case of gastrointestinal myiasis in a 15 year-old rural Moroccan girl. She was admitted for abdominal pain, hematemesis, and worm vomitting. The parasitologic identification revealed Sarcophaga hemorrhoidalis. Through this observation, the authors underline the epidemiological, clinical and evolutive aspects of this parasitosis in Morocco.

Epidemiology of human visceral leishmaniasis in Taounate, a northern province of Morocco.

We report the preliminary results of an epidemiological survey carried out in the locality of Ouled Hcein, province of Taounate (North Morocco) around one visceral leishmaniasis infant case. The strain isolated from the child was characterized by three methods as Leishmania infantum and its isoenzyme pattern was indistinguishable from zymodeme MON-1. The human survey in the locality of origin of the index case did not show any additional case and the serology was negative for the whole people sampled. The canine survey showed that the highest seroprevalence of the canine disease was found in the locality of Ouled Hcein (27.1%) when compared to 4 surrounding localities. The entomological survey showed that amongst the demonstrated L. infantum vectors around the Mediterranean Basin, Phlebotomus longicuspis was the predominant species. Furthermore, the survey led to the identification of one female of P. ariasi naturally infected with L. infantum, so this species should be at least one of the vectors of this parasite in this area. Thus, this study confirms that the transmission cycle of L. infantum in North Morocco is similar to the cycle found in the remaining Mediterranean area.

Cutaneous leishmaniasis: an emerging epidemic focus of Leishmania tropica in north Morocco.

Cutaneous leishmaniasis in Morocco occurs mainly in the south and is caused by Leishmania major and L. tropica. In 1995, for the first time, 4 autochthonous cases were confirmed by smear and/or culture from the province of Taza in north Morocco. An active survey revealed 128 more cases. The number had increased gradually since 1994. Most of the cases (86%) came from the suburbs of the city of Taza. All cultured and typed parasites were characterized as L. tropica MON-102. A leishmanin skin test survey among a random sample of the exposed population showed an overall positivity rate of 19.9%, with no correlation with age or gender. The spatial distribution of the cases and skin test positivity, their occurrence in all age groups, the highly variable clinical picture, the severity and large size of lesions in older patients, the slow recovery of some treated patients, and the isoenzymic monomorphism of the parasite, all suggested that cutaneous leishmaniasis caused by L. tropica is an emerging disease in Taza.

[Ileocecal tuberculosis. Apropos of 27 cases]. / La tuberculose iléo-caecale. A propos de 27 cas.

The authors report a retrospective study of 27 cases of "ileo-caecal tuberculosis" collected over a period of 10-years. Sixteen women and eleven men, between 14 and 55 years of age (with a group mean age of 28 years), were included. This is still a common disease in Morocco, despite attempts to achieve universal BCG vaccination. Diarrhoea, abdominal pain and a general physical deterioration are the most indicative signs, but are not specific. Tests for M. tuberculosis hominis are often negative, except in cases in which bacteria proliferate in pulmonary excavations, and this makes it difficult to establish a definite diagnosis. The detection of narrowing of the ileum or colon in a country where infection is endemic suggests the possibility of tuberculosis. Colonoscopy, which is becoming increasingly widespread in Morocco, makes an essential contribution. Although it is rare for caseum to be detected in biopsy fragments, the main value of histopathology is that it can eliminate cancer, making it possible to start antibacterial treatment without a diagnostic laparotomy. The outcome of medical treatment is nearly always positive. Clinical improvement, bacteriology tests and X-ray examinations are criteria that a cure has been obtained.

Scorpion venom cardiomyopathy.

Cardiac function was evaluated by serial echocardiography in 30 children affected by scorpion stings. They could be separated into two groups on the basis of the initial echocardiogram. Group 1, consisting of 18 children, had normal left ventricular function, whereas group 2, consisting of 12 children, showed compromised left ventricular function (ejection fraction less than 0.55; fractional shortening less than 27%). In group 2 the left ventricular end-systolic dimension was increased significantly and the interventricular septal thickening fraction was depressed significantly, compared with group 1. Nine children in group 2 showed improvement in all measurements of contractility, usually within 24 to 48 hours. Of the remaining children, one showed no echocardiographic changes and subsequently died. Another child made a slow improvement over several weeks. We conclude that myocardial toxicity is a common and serious complication of scorpion stings in children. Systolic function appears to be affected predominantly. Serial echocardiography is useful to follow changes in left ventricular function, which are generally matched by clinical improvement. Patients who fail to improve within 24 to 48 hours require particularly close observation.