Malignant Hypercalcemia Revealing Pulmonary Sarcoidosis.

Sarcoidosis is a systemic disorder characterized by the development of granulomatous inflammation in various organs of the body. Hypercalcemia is one of its manifestations. We present a case of malignant hypercalcemia in a 77-year-old man, diagnosed as sarcoidosis following multiple assessments and histological confirmation showing noncaseating granulomas. In the absence of an etiological diagnosis, treatment was initially based on hydration, diuretics, and bisphosphonate. Glucocorticoid therapy can be the standard treatment for hypercalcemia related to sarcoidosis.

Aripiprazole dose associations with metabolic adverse effect: Results from a longitudinal study.

OBJECTIVE: Weight gain, blood lipids and/or glucose dysregulation can follow aripiprazole treatment onset. Whether aripiprazole dosage is associated with an increase in these metabolic parameters remains uncertain. The present study investigates aripiprazole dose associations with weight change, blood glucose, lipids, and blood pressure. METHODS: 422 patients taking aripiprazole for a minimum of three weeks to one year were selected from PsyMetab and PsyClin cohorts. Associations between aripiprazole dose and metabolic outcomes were examined using linear mixed-effect models. RESULTS: Aripiprazole dose was associated with weight change when considering its interaction with treatment duration (interaction term: -0.10, p < 0.001). This interaction resulted in greater weight gain for high versus low doses at the beginning of the treatment, this result being overturned at approximately five months, with greater weight increase for low versus high doses thereafter. LDL and HDL cholesterol levels were associated with aripiprazole dose over five months independently of treatment duration, with an average of 0.06 and 0.02 mmol/l increase for each 5 mg increment, respectively (p = 0.033 and p = 0.016, respectively). Furthermore, mean dose increases were associated with greater odds (+30 % per 5 mg increase) of clinically relevant weight gain (i.e., ≥7 %) over one year (p = 0.025). CONCLUSION: Aripiprazole dose was associated with one-year weight changes when considering its interaction with treatment duration. Increasing its dose could lead to metabolic worsening over the first five months of treatment, during which minimum effective doses should be particularly preferred.

Lung Sarcomatoid Carcinoma: An Intriguing Case Report of a Rare Malignancy.

Sarcomatoid carcinoma (SC) is a rare primary malignant tumor belonging to the group of non-small cell lung cancer (NSCLC). The diagnosis requires proper tumor sampling to exclude sarcoma, which is the main differential diagnosis. However, the prognosis of these tumors is poor, with a median survival rate lower than other NSCLC cases, mainly due to their aggressiveness and resistance to chemotherapy, especially platinum salts. In this report, we discuss a case of a 62-year-old male patient who presented at admission with hemoptysis and dyspnea. The diagnosis process involved thoracic computed tomography (CT) and fiberoptic bronchoscopy, which revealed tissue thickening at the carina and a mass extending from the lower end of the trachea to the carina, which was confirmed by biopsy. Unfortunately, despite receiving neoadjuvant radiotherapy and having endotracheal prosthesis, the patient succumbed to tumor progression. Our case highlights the aggressive nature of this tumor and underscores the importance of early detection.

Pleurisy as a Sign of Chronic Lymphocytic Leukemia.

The diagnosis of chronic lymphoid leukemia (CLL) is essentially based on a blood smear and immunophenotyping by flow cytometry of circulating lymphocytes. Unusual locations of the disease can sometimes be observed. Here we report the case of a patient admitted for the management of pleurisy. The pleural effusion was lymphocytic exudate; histological examination of the pleural biopsy along with immunohistochemistry helped yield the diagnosis of secondary localization of CLL. The patient was transferred to the Internal Medicine department where chemotherapy was introduced.

Checklist of ladybirds of Algeria with two new recorded species (Coleoptera, Coccinellidae).

An updated and corrected checklist of species of ladybird beetles (Coleoptera: Coccinellidae) known in Algeria now contains 75 species belonging in ten tribes. New country records include the European species Oenopia conglobata and the invasive Asian species Harmonia axyridis. Sampling data is provided for 14 species found during a faunistic survey performed mostly in agroecosystems, together with host plant and prey species.

Fatal Kounis syndrome with stent thrombosis secondary to amoxicillin/clavulanic acid use: A case report and literature review.

Anaphylactic reactions are often induced by drugs, and the most frequent ones are penicillin derivates. The concurrence of acute coronary syndrome with hypersensitivity and anaphylactic or anaphylactoid reactions constitutes the Kounis syndrome. We report a case of a coronary stent thrombosis with a fatal outcome complicating an anaphylactic shock induced by amoxicillin-clavulanic acid association. A 58-year-old woman with a history of triple coronary stenting was treated by amoxicillin/clavulanic acid association for pharyngitis. One hour after the first drug intake, she developed an anaphylactic shock with acute constricting chest pain. She received intravenous hydrocortisone and was transferred to emergency department. The patient received epinephrine intravenously with fluid perfusion and oxygen. Electrocardiogram showed Pardee waves in the anterior precordial leads. Cardiac enzyme levels (troponin I) were disturbed. The patient was transferred to the coronary care unit with a diagnosis of acute myocardial infarction. The coronary angiography revealed anterior interventricular stent thrombosis. The patient experienced a cardiogenic shock with an important hemodynamic repercussion, and she died few hours later despite emergency care. The responsibility of amoxicillin-clavulanic acid association was retained in the genesis of this anaphylactic shock in front of a suggestive delay, a compatible evolution and a high semiotic score. Amoxicillin/clavulanic acid use may cause Kounis syndrome. The use of epinephrine is a challenging decision. We suggest that Kounis syndrome should be considered in the differential diagnosis of acute coronary syndrome.

Protective effect of Ulva lactuca extract during hepatic cold preservation in rats.

Introduction In recent years, many marine resources have drew attention in the research for bio-active compounds to develop new drugs and health foods. (1) Marine algae are now considered as a rich source of antioxidants (2). It is known that seaweeds contain numerous bioactive substances that have the ability to lower cholesterol, reduce blood pressure, promote healthy digestion; and antioxidant activity (3). Natural antioxidants are interesting compounds due to their properties which help prevent oxidative stress (4), among other potentially beneficial actions. For instance, several biological effects have been attributed to flavonoids, such as anti-tumoral, anti-inflammatory, anti-ischemic and anti-aggregate plaquetary activities. These activities are believed to be in part related to the antioxidant properties of the compounds, namely in scavenging radical oxygen species (ROS). (5, 6) The cold ischemia constitute a situation of oxidative stress in touch with liberation of oxygenated radicals, these situations incited the researchers to find means for the improvement of the conservation of organs allowing to prolong the durations of the cold ischemia of certain organs (in particular the liver) with conservation of the maximum functional value. However, the constant efforts led by the teams of transplantation to develop transplants, the conservation of organs remains a problem to be resolved. (7) Conservation solution of organ appears as being a stemming to remedy the fatal effects of the ischemia-reperfusion. For our part, we think that seaweeds have not delivered their secrets and yet especially that the marine environment of the Tunisian coast still remains little exploited in spite of the big variety of the fauna and the flora of the coast. We envisage in this work, to study a sort of seaweed collected on the Tunisian quotation in the region of "Chott Meriem" (North West of Tunisia). The purpose of our work is to estimate the capacity of extracts stemming from the green seaweed Ulva lactuca to improve the conservation solution of organs against the hepatic effects of ischemia.

Animal model of liver ischemia reperfusion: biochemical and histological evaluation.

INTRODUCTION: During last years, significant progress was made in the comprehension of the hepatic lesions after Ischemia-Reperfusion episode in order to improve the Results in practice clinical. AIM: To avoid or reduce the damage induced by Ischemia-Reperfusion, we developed a model of hepatic Ischemia-Reperfusion with variable periods of reperfusion from 0 to 24 hours.  METHODS: Our study related to rats Wistar males.  Six various groups were studied: the first reference group (without neither ischemia and reperfusion), the second group with ischemia of 90 min and without reperfusion and the 3end , 4end, 5end and 6end groups in addition to ischemia, underwent a reperfusion of 30 min, 2h, 6h and 24h respectively.  The damage of hepatic Ischemia-Reperfusion was evaluated by a biochemical test based on the proportioning of transaminases and an anatomopathologic study by optical microscopy for the determination of the degree of hepatic attack.  RESULTS: The RESULTS obtained seem to show an aggravation of the liver lesions and an increase in the plasmatic rates of AST and ALT in relation with the duration of the reperfusion.  Indeed, the maximum of damage was observed after 2 hours of reperfusion. We observed a reduction in the lesions after 6h and 24h of reperfusion.  CONCLUSION: Our work enabled us to describe a simple model of hepatic Ischemia-Reperfusion with functional, biochemical and anatomopathologic tests.

[Comparative study of two techniques of ciclosporine monitoring]. / Étude comparative de deux techniques de dosage de la ciclosporine.

Ciclosporine (CsA) is an immunosuppressant drug used in bone marrow transplantation in order to extend allograft survival. Despite its efficiency, CsA can expose to therapeutic failure or to toxicity because of underdosing or overdosage. So, many techniques of monitoring CsA in blood were used, the referance one is the chromatographic technique then, the automated techniques: fluorescence polarization immunoassay (FPIA) and chimiluminescent microparticle immunoassay (CMIA). In this study, we aimed to compare the results of CsA concentrations measured by the two automised techniques. Statistical studies showed that the two techniques were repeatable and reproductible. Results obtained by FPIA were slightly higher than those obtained by CMIA but without a significative difference. In conclusion, FPIA technique could be used to measure CsA blood concentration in replacement of CMIA in case of technical problems.

Contribution of Therapeutic Monitoring in the Assessment of Toxic Adverse Effects of Mitotane: a Case Report.

Mitotane provided serious side effects and low doses seemed to be tolerated. Determination of mitotane concentration in plasma is recommended. We report the case of toxic plasma levels with low doses of mitotane in a 47-year-old man with adrenocortical cancer.

[Therapeutic Drug Monitoring of Valproic Acid in Children: A Prospective Study of The Effect of The Compliance and The Economic Level on the Trough Plasmatic Concentrations and Epileptic Seizures]. / Suivi thérapeutique de l'acide valproïque chez l'enfant : étude prospective de l'effet de l'observance et du niveau économique sur les concentrations plasmatiques résiduelles et les crises épileptiques.

INTRODUCTION: Valproic acid (VA) is a widely used antiepileptic drug. Because of its pharmacokinetic variability and the influence of intrinsic and extrinsic factors such as the treatment compliance, VA therapeutic drug monitoring (TDM) is recommended in children. The aim of this study is to evaluate the effect of treatment compliance and the economic level on VA tough plasmatic concentration (TPC) and epileptic rhythm in children. MATERIAL AND METHODS: A one-year prospective study (August 2008-August 2009) concerning children (age≤5 years) regularly treated by VA who had a VA TDM. So, 276 plasmatic samples from 238 children were collected. The children were divided in two groups as following: the group 1 (G1) presenting a good compliance and a reliable questioning and the group 2 (G2) presenting a bad compliance and a non reliable questioning. We evaluated the interindividual variability by correlating the TPC to the dose. Then, we divided the hole group in function of their economic levels (low-medium-high). RESULTS: Sex ratio male/female was 1.3. Median age was 5 years+/-3,9. The mean TPC was 62 µg/mL [0.12-131 µg/mL]. VA TPC were in the therapeutic range (TR) in 62%. Adverse drug reactions were noted in 4.2% of the children. G1 represented 70% of the children and G2, 30%. The TPC were in the TR in 67% of G1 and 51% of G2 (p=0.02). There was a significant difference between the TPC in G1 and G2 (p=0.02).There was no significative difference in the TPC in function of the economic levels. There was no correlation between TPC and the administered doses. The epileptic seizures were more spaced in children with therapeutic TPC than those with TPC in the TR (p=0.002) and in G1 than in G2 (p=0.03). CONCLUSIONS: Compliance should be appropriate in order to optimize the TDM rule. A good compliance and a therapeutic TPC allow a better control of epileptic seizures.

Involvement of CYP 3A5 In the Interaction Between Tacrolimus and Nicardipine: A Case Report.

Tacrolimus is a calcineurin inhibitor primarily metabolized by CYP3A4 and secondarily by CYP3A5. Several drugs can modify tacrolimus blood levels as calcium channel blockers (CCBs). Interaction with nicardipine was reported in some cases. A man with a history of malignant arterial hypertension treated with nicardipine, underwent kidney transplantation. After transplantation, he was treated with tacrolimus, mycophenolate mofetil and corticoids. Therapeutic drug monitoring of tacrolimus was done regularly showing a mean trough concentration (C0) of 24.39 ng/mL with some concentrations reaching 52 ng/mL. After changing nicardipine by prazosine, the first tacrolimus C0 after stopping nicardipine was 3.2 ng/mL. Increase of tacrolimus trough concentrations is due to the inhibition of CYP3A4. Very high levels of tacrolimus suggest the non expression of CYP3A5. Thus, because of the possible lack of the secondary pathway, therapeutic drug monitoring of tacrolimus is highly recommended at the introduction of CCBs and also at its stopping.

[Development and validation of a new HPLC method for determination of Lamotrigine and clinical application]. / Mise au point validation d'une method de dosage de la lamotrigine par chromatographie liquid à haute performance et application clinique.

BACKGROUND: Lamotrigine is an effective anticonvulsant drug used in the treatment of epilepsy. It has a narrow therapeutic range, a large inter and intra-individual pharmacokinetic variability and some concentration-dependent side effects. AIM: The aim of this study was to develop and validate a new method for lamotrigine quantitation in plasma using HPLC with UV/visible detection. METHODS: A rapid HPLC-UV method was developed for the determination of lamotrigine in plasma. All solvents used were HPLC grade. RESULTS: After liquid-liquid extraction, chromatographic separation was achieved using an RP 18 (250 mm) column. The mobile phase was composed of acetonitrile and 0.1 M potassium dihyrogenophosphate (25/75) (v/v). Barbital sodium was used as internal standard. This technique was linear over the 2 µg/mL to 50 µg/mL range (r= 0.99). Detection and quantification limits were 0.07 µg/mL and 0.21 µg/mL, respectively. Within-day coefficient of variation (13.37 to 16 %) and day-to-day coefficients of variation (15.68 to 16.63 %) at three different concentrations. Under these conditions, each analysis required no longer than 10 min. We finally evaluated the plasma concentrations of lamotrigine in Tunisian patients treated with this drug. CONCLUSION: The results found are similar to those previously described and the developed method is repeatable and reproducible. It can be used for clinical applications.

Pharmacokinetik population of methotrexate in tunisian population with acute lymphoblastic leukemia.

BACKGROUND: The use of high dose of MTX in the treatment of the leukemia is actually better controlled by renal preparation, control of plasma concentrations and administration of folinic acid. However, High dose MTX has been proven to cause substantial toxicity and have high intra-and inter-patient variability. Population pharmacokinetic analysis is a useful tool for identification of sources of pharmacokinetic variability during anticancer drug development and can aid the design of alternative dosing regimens to enhance their efficacy and safety. AIM: The aim of our study is to developed and validate a population pharmacokinetics model of our population. We hereby describe the clinical covariates (age, sex and clearance of the creatinine) that influence MTX pharmacokinetic for predicting optimal dose to reduce MTX toxicity. METHOD: It is a prospective study achieved between January 2005 to January 2012 in the Service of Clinical Pharmacology. Including 273 patients treated for acute lymphocytic leukaemia 2582 plasma concentration was achieved. The data have been analyzed with Nonmem© software (non linear regression to mixed effect). RESULTS: The age of our patients varied from 2 to 23 years with an average of 13 years. The patients received high dose MTX therapy (1 to 8 g/m2) in 24 hours infusion every 15 days. Three compartiment models describe the pharmacokinetic of MTX. The most important covariables affecting the model were clearance of the creatinine, age and weight. We obtained a good correlation between the predicted and the observed concentrations. CONCLUSION: The development of population pharmacokinetics model of MTX allows us to propose a therapeutic diagram adapted to every patient according to its morphological and pharmacological features while taking in consideration the therapeutic objective.

Probable disseminated BCG infection in a 10-month-old child after BCG vaccination.

The disseminated BCG infection is a rare and serious complication of bacillus Calmette-Guerin (BCG) vaccine. We report a case of probable disseminated BCG infection in a 10-month-old child who had been vaccinated by BCG vaccine at birth. No incident was noted on the first days of vaccination. At the age of 40 days, she developed left supra clavicular and axillar abcessed lymph nodes. She was treated by surgical flattening of the lymph adenopathy. The same lymph node recurred at the age of 6 months and was treated with surgery. Few weeks after the second episode, cutaneous ulcerative lesions appeared. Cutaneous biopsy was performed and showed lesions compatible with tuberculosis. X-rays showed osteolysis of P1 of the middle finger in the left hand. She was treated by anti-tuberculosis antibiotics.

Vancomycin therapeutic drug monitoring in cerebrospinal fluid.

Vancomycin penetrates poorly through the blood-brain barrier. Determination of vancomycin concentration in plasma is recommended. In contrast, its determination in cerebrospinal fluid (CSF) is rarely performed. We report the case of a 74-year-old man with post traumatic meningitis with vancomycin concentration measured in CSF.

Means of evaluation and protection from doxorubicin-induced cardiotoxicity and hepatotoxicity in rats.

OBJECTIVES: This work is aimed on the study of doxorubicin cardiotoxicity and hepatotoxicity in rats and the evaluation of protective effect of trimetazidine administrated concomitantly with doxorubicin for 3 days. MATERIALS AND METHODS: Male Wistar rats used were subjected to different types of treatment (3 days); A: Control, B: Doxorubicin treatment and C: Trimetazidine and doxorubicin treatment. After sacrifice, tissular distribution of doxorubicin, cardiac scintigraphy, histological examination of the myocardium, and evaluation of liver function were assessed. RESULTS: Obtained results show that doxorubicin has a high affinity to tissues especially the heart. It causes hepatotoxicity and cardiotoxicity marked by a significant increase of aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) levels and drop of the left ventricular ejection fraction (EF LV ) by scintigraphy. Histological examination showed general alteration of myocardium structure. Concomitant administration of trimetazidine attenuates significantly the cardiotoxicity and hepatotoxity induced by doxorubicin. CONCLUSION: We have evaluated the protective effect of trimetazidine on an animal model of doxorubicin-induced cardiotoxicity and hepatotoxicity. The evaluation of these effects were assessed by several means; tissular distribution of doxorubicin, histological examination, assessment of liver function, and EF LV by scintigraphy that characterizes the originality of this study.

Lichen associated with metformin.

We report an exceptional case of bullous lichen induced by metformin in a patient with diabetes mellitus.