Serum drug concentrations of INH and RMP predict 2-month sputum culture results in tuberculosis patients.

BACKGROUND: In Alberta provincial tuberculosis (TB) clinics, serum drug concentrations (SDCs) are measured in patients with human immunodeficiency virus, diabetes mellitus or at extremes of weight, or showing slow clinical response to treatment, to guide treatment. DESIGN: A retrospective review was performed of TB cases in Northern Alberta with SDCs measured from 1998 to 2013. Adequacy of SDC was based on the maximum concentration (Cmax) achieved in serum, with rifampicin (RMP) values <8 µg/ml and isoniazid (INH) values <3 µg/ml for daily dosing and <9 µg/ml for intermittent dosing considered inadequate. Clinical variables and microbiological outcomes were then compared between the adequate and inadequate groups. RESULTS: Of 134 pulmonary TB cases with SDCs for INH and/or RMP, we found a significant increase in 2-month sputum culture positivity in the cohort with inadequate concentrations of INH compared to those with adequate INH concentrations (42.5% vs. 18.3%, P = 0.0084). A similar trend was seen in the cohort with inadequate concentrations of RMP (39% vs. 21%, P = 0.0725). CONCLUSIONS: Among our study population, low SDCs of INH and, to a lesser extent, RMP, appear to be associated with reduced sputum culture conversion after 2 months of treatment.

Effect of Aloe vera preparations on the human bioavailability of vitamins C and E.

There are no literature references describing the effect of consumption of Aloe vera liquid preparations on the absorption of water- or fat-soluble vitamins. There is a very large population worldwide which consume vitamins and many people also consume Aloe. Thus we report the effect of Aloe on the human absorption of vitamins C and E, the most popular vitamin supplements. The plasma bioavailability of vitamins C and E were determined in normal fasting subjects, with eight subjects for vitamin C and ten subjects for vitamin E. In a random crossover design, the subjects consumed either 500 mg of ascorbic acid or 420 mg of vitamin E acetate alone (control), or combined with 2 oz of two different Aloe preparations (a whole leaf extract, or an inner fillet gel). Blood was collected periodically up to 24 h after consumption. Plasma was analyzed for ascorbate and tocopherol by-HPLC with UV detection. There was no significant difference in the areas under the plasma ascorbate-time curves among the groups sincerely due to large differences within the groups. For comparative purposes the control area was 100%. The Aloe Gel area was 304%, and Aloe Whole Leaf 80%. Only Aloe Gel caused a significant increase in plasma ascorbate after 8 and 24 h. For vitamin E, the results for the relative areas were control 100%, Gel 369%, and Leaf (198%). Only the Aloes produced a significant increase in plasma tocopherol after 6 and 8 h. Both Aloes were significantly different from the control after 8 h. Aloe Gel was significantly different from the baseline after 24 h. The Aloes slowed down the absorption of both vitamins with maximum concentrations 2-4 h later than the control. There was no difference between the two types of Aloe. The results indicate that the Aloes improve the absorption of both vitamins C and E. The absorption is slower and the vitamins last longer in the plasma with the Aloes. Aloe is the only known supplement to increase the absorption of both of these vitamins and should be considered as a complement to them.

Investigation of the spread of human visceral leishmaniasis in central Tunisia.

The epidemiology, clinical patterns, and spatial spread of Mediterranean visceral leishmaniasis were retrospectively studied in central Tunisia. The clinical profile of the disease was typical of the Mediterranean infantile form. Malnutrition and associated infectious diseases were observed in 62.5% and 55% of cases, respectively. The case-fatality rate was 6.2% and resistance to meglumine antimonate was observed in 1.6% of patients. The annual incidence of cases increased from approximately 10 cases per year before 1991 to approximately 50 cases per year between 1992 and 1994. The cumulative incidence was 133.7/100,000 among children aged < 15 years. This increase was preceded by 3 years of high mean annual rainfall in the region. The spatial distribution of the incidence of the infection through time showed an aggregation of cases in the northern part of the area where intensive agriculture projects took place during the last 10 years, leading to the establishment of a stable Leishmania infantum transmission cycle below the Atlas mountain chains, and an evident tendency to a progressive extension to the south.

Evaluation of antivenom therapy in children severely envenomed by Androctonus australis garzonii (Aag) and Buthus occitanus tunetanus (Bot) scorpions.

One hundred and forty-seven cases of envenomed children under 15 years old presenting local and general symptoms without failure in vital functions (clinical grade II) or presenting serious general symptoms with failure in vital functions (clinical grade III) were collected during the summer seasons of 1993-1997. They were classified in six groups according to the use or not of antivenom, the route and the frequency of antivenom administration. The determination, by a sensitive ELISA, of blood venom concentration before and until 6 h after antivenom therapy, allowed the establishment of the venom toxicokinetic curve for each group. The intramuscular administration of antivenom did not show significant effects on venom toxicokinetic curves and on patients recovery time. However, the same amount of antivenom administered by intravenous route clear rapidly the blood free venom toxins. Also, the patient recovery time was significantly shortened. These data are in favor of intravenous application of an adequate dose of an efficient antivenom in order to treat successfully severe scorpion envenoming cases.

Usefulness of exercise echocardiography in predicting cardiac events in an outpatient population.

The prognostic value of exercise echocardiography in an outpatient population is not well defined. A total of 1,020 consecutive patients referred for exercise echocardiography in an ambulatory care setting were studied by reviewing their medical records and exercise echocardiographic data. Of these, 71 (7%) were excluded due to technically inadequate tests, leaving 949 patients who were included in the analysis. A positive exercise echocardiogram (EE) was defined as an appearance of a new wall motion abnormality or worsening of a baseline abnormality. Cardiac events, defined as myocardial infarction, coronary angioplasty, coronary bypass surgery, and death, were documented during a 12-month follow-up period. Cardiac events occurred in 17% of patients (26 of 152) with a positive exercise echocardiogram (EE) and in 2.5% (20 of 797) with a negative EE (p <0.001). The incidence of myocardial infarction (2.6% vs 0.4%, p <0.02), coronary angioplasty (7% vs 1%, p <0.001), and coronary bypass surgery (9% vs 1%, p <0.001) were higher in patients with a positive versus a negative EE. There was 1 death in the positive study group and none in the negative group. Significant independent variables (p <0.05) that predicted cardiac events included a positive exercise electrocardiogram, history of coronary angioplasty, nonspecific ST-T changes on the baseline electrocardiogram, double product <25,000, men, chest pain on exercise test, and a positive exercise electrocardiogram. On a stepwise logistic regression model, exercise echocardiography emerged as an independent predictor of future cardiac events in an outpatient population. This predictive value was enhanced in the presence of a positive exercise electrocardiogram compared with a negative exercise electrocardiogram (24.2% vs 7.9%, p <0.03). Our study suggests that exercise echocardiography is an independent predictor of future cardiac events in an outpatient population.

Development of an ELISA for the detection of scorpion venoms in sera of humans envenomed by Androctonus australis garzonii (Aag) and Buthus occitanus tunetanus (Bot): correlation with clinical severity of envenoming in Tunisia.

A sandwich ELISA was set up for measuring scorpion venom levels in sera of accidentally envenomed humans with the aim to establish a quantitative relationship between these levels, envenoming severity and clinical symptoms. This assay used equine polyclonal F(ab')2, specific to two North African scorpion (Androctonus australis garzonii: Aag and Buthus occitanus tunetanus: Bot) venoms. The test proved to be simple, reproducible, very sensitive (detection limit = 0.9 ng/ml) and linear between 0.5 and 15 ng/ml of venom concentrations. A large survey on scorpion sting envenomings was conducted from 1993 to 1996 in Tunisia to gather accurate epidemiological, clinical and biological data from victims as well as informations on the treatment that they had received. Victims were classified into three grades (GI, GII and GIII) of increasing severity according to clinical signs of envenoming. Blood samples were collected from victims and tested by ELISA for their content of Aag and Bot venoms. A strong correlation was found between clinical symptoms of envenoming and the level of scorpion venom antigens in serum (r = 0.980). Mean serum venom concentrations were: 2.65 +/- 0.81 ng/ml in GI envenoming, 9.79 +/- 4.08 ng/ml in GII and 21.7 +/- 6.51 ng/ml in GIII. The difference between each group was statistically significant (p < 0.01). This ELISA may prove to be helpful to establish a rationale approach of specific antivenom therapy.

Cholinergic control of catecholamine release in the eel.

The perifused posterior cardinal vein of the American eel (Anguilla rostrata) releases spontaneously dopamine (DA), norepinephrine (NE), and epinephrine (E). NE and E are secreted by innervated chromaffin cells, while DA is most likely released from a component of the vascular wall. Stimulation with acetylcholine strongly enhances the release of DA and E, and to a lesser degree the release of NE. Nicotine stimulates the release of all three catecholamines. Muscarine reduces the basal release of NE. Muscarine does not prevent nicotinic stimulation of NE and E release, but abolishes the nicotine effect on DA release. The muscarinic antagonist atropine stimulates the release of NE, but not of DA and E. The beta-adrenergic receptor antagonist propranolol suppresses the acetylcholine-stimulated release of NE and E, and reduces the DA response. From these findings, it appears that (1) nicotinic receptors regulate NE and E secretion from the chromaffin cells, (2) muscarinic receptors inhibit basal NE release, and (3) acetylcholine-stimulated release of NE and E requires the interaction with adrenergic receptors. On the other hand, DA release involves both nicotinic and adrenergic receptors, while the reduction of nicotine-stimulated (but not basal) DA release involves muscarinic receptors.

Opioid effects on macrovascular dopamine release.

Both alkaloid opiates and met-enkephalin occur in vertebrate chromaffin cells, where they affect catecholamine (CA) secretion. Since the large blood vessels of the eel and the rat release dopamine (DA) from as yet unidentified source(s), we studied the impact of alkaloid opiates and met-enkephalin on the secretion of DA from three macrovessels of the American eel (Anguilla rostrata) in a perifusion system. Codeine, morphine, and met-enkephalin increased the release of DA from both the ventral aorta and the caudal vein. The antagonist naloxone stimulated DA release from the caudal vein, but had no impact on release from the ventral aorta. Only codeine had a significant effect on DA release from the posterior cardinal vein. These findings show that the DA release from the macrovessels is sensitive to opioid substances, and they suggest that the antagonistic effects between alkaloid opiate and opioid peptide, seen in other systems, are absent in large blood vessels. Furthermore, the "unorthodox" stimulatory effect of naloxone in the caudal vein raises the question of as yet unidentified receptor and/or effector systems.

[Screening of hemoglobinopathies and molecular analysis of beta-thalassemia in Central Tunisia]. / Dépistage des hémoglobinopathies et analyse moléculaire des beta-thalassémies en Tunisie centrale.

BACKGROUND: Previous investigations have permitted to locate 16 beta-thalassemic mutations in different samples of the Tunisian population. One of them (IVS I nt 2: T--G) had been found only in the central region of Tunisia. Our research was carried out in this part of the country to estimate the prevalence of this mutation and to establish a prenatal diagnosis using appropriate probes. POPULATION AND METHODS: One thousand one hundred and five blood samples taken from 1987 to 1990 from healthy blood donors and 346 samples taken from 1985 to 1992 from patients were analysed. Detection of hemoglobinopathies was carried out by means of specific hematological tests and different electrophoretic and chromatographic techniques. Mutations were detected by means of the usual techniques of molecular biology. RESULTS: Sickle cell anemia and beta-thalassemia were the most frequent in the samples studied. The molecular analysis carried out on eight patients native of the Essouassi-El-Djem region point out that all these patients carry the same point mutation (IVS I nt 2: T-G) detected for the first time in 1988 in a patient native of the same region. One of these patients, aged 43, who did not suffer from anemia and did not show the usual symptoms of beta O thalassemia, had one hemolytic attack at the age of 17. CONCLUSIONS: The high number of persons carrying Hb S and beta-thalassemia trait increase the risk of appearance of homozygous forms. The presence of the same mutation IVS I nt 2: (T-G) in all beta O-thalassemic patients from Essouassi-El Djem region may indicate that it may have its origin there. The heterogeneity of clinical phenotype of these patients shows the difficulty of establishing a unique strategy of prenatal diagnosis by DNA analysing which can be applied in all cases.

[Partial splenectomy in thalassemia major. Apropos of 19 cases]. / La splénectomie partielle au cours des thalassémies majeures. A propos de 19 cas.

Nineteen cases of B Thalassemia have benefited from partial splenectomy at the General Surgery Service of Farhat Hached Hospital in Sousse (Tunisia). The partial splenectomy indication was to reduce hypersplenism, thus transfusion needs, to suppress splenic pain and to conserve a splenic remnant, which preserves patients' immunity. The operation was in reality a subtotal splenectomy keeping the lower pole in all cases. We had no per-operatory complication. The preoperatory bleeding was not more serious than in total splenectomy. In all the patients, we noticed reduction of about half the transfusion need, except one who had also a chronic deficit in glyco-six phospho-dehydrogenase. The average hemoglobin rate increased from 60 g/L in the pre-operatory to 80 g/L after the operation. Consequently, this reduction of transfusion needs results in the decrease of the hemochromatosis, which is one of the main complications of hypertransfused thalassemia.

[Recessive osteopetrosis. Identification of a form of medium severity]. / La forme récessive de l'ostéopétrose. Individualisation d'une forme de gravité intermédiaire.

BACKGROUND: Several distinct forms of osteopetrosis have been identified. Some of the autosomally recessive inherited forms are benign, much like the autosomal dominant form. Others are more malignant. PATIENTS: The clinical data, skeletal radiographs, histological features and histories of 32 children with osteopetrosis were analyzed retrospectively. RESULTS: The 32 patients, belonging to 20 sibships were divided into two groups. The first group included 24 patients, aged 1 day-11 months (mean 4.5 months), suffering from hepatosplenomegaly, anemia, thrombocytopenia and optic atrophy in early infancy. They also had a generalized increase in bone density, abnormal bone remodeling, rachitic lesions and a "bone-within-bone" appearance. Biopsies showed severe bone resorption and myelofibrosis. 19 of the 20 patients whose outcomes were known died during the first year of life. The second group included 8 patients, aged 40 days-3 years (mean: 11 months). Hepatosplenomegaly appeared later, anemia was less severe and thrombocytopenia occurred in only 1 patient. However, all 8 patients suffered from optic atrophy and 3 were deaf. Radiographs showed bone growth without rachitic lesions. Biopsies from 2 patients showed bone resorption, but no myelofibrosis. The outcome was less severe: 6 patients, now aged 8 months to 8 years, have survived, 3 of them for over 5 years. Genetic investigation showed patterns compatible with autosomal recessive inheritance in both groups, with similar sets of features within each sibship. CONCLUSION: This study reveals a new type of recessively inherited osteopetrosis. It can be classified as an intermediate form, distinct from both the malignant and the benign forms, and also distinct from osteopetrosis with carbonic anhydrase II deficiency.

[Cirrhosis and cirrhogenic diseases in Tunisian children. Multicenter study of 65 cases]. / Les cirrhoses et les maladies cirrhogènes de l'enfant tunisien. Etude multicentrique de 65 cas.

Over a period of 10 years, 65 cases of hepatic cirrhosis and cirrhogenic disease have been observed in five Pediatric Centers in mid Tunisia. The age of the patients ranged from 30 days to 14 years. The main etiology was biliary cirrhosis (24 cases) followed by post-hepatic cirrhosis (15 cases). Eight cases had a metabolic origin, which was Wilson's diseases in five cases. Three children had cirrhosis of a pre-hepatic origin. In 15 children, the liver biopsy showed the presence of cirrhosis but the etiology could not be found. Preventive measures are needed in order to reduce the frequency of cirrhosis among Tunisian children: 1) early recognition of biliary atresia, 2) vaccination against hepatitis B virus of at risk neonates and children, 3) Genetic counselling and search for familial cases when cirrhosis of metabolic origin is identified, particularly Wilson's disease.

[4p trisomy secondary to paternal translocation t(4p-;15q+)]. / Trisomie 4p secondaire à une translocation paternelle t(4p-;15q+).

A new case of trisomy 4p is reported. The patient was a boy with dysmorphism, growth failure and developmental retardation. Craniofacial features included microcephaly with a flat forehead, a prominent glabella, hyperteleorism, a broad, concave nasal bridge, a bulb-shaped nose, a wide mouth with a prominent upper lip and a short philtrum, low-set ears, a low hairline, micrognathia, and a short neck. Abdominal muscles were normal. Cryptorchidism with a hypoplastic scrotum and a micropenis were found, as well as forced flexion of the fingers and talipes equinus. The intravenous urogram disclosed ptosis of the right kidney. Developmental retardation was severe with an IQ under 50. RHG banding techniques on peripheral lymphocytes disclosed 4p14 pter duplication. The karyotype was 46,XY inv dup(4-p) (p14----pter). The mother's karyotype was normal. The father had a translocation between the short arm of chromosome 4 and the long arm of chromosome 15; his karyotype was 46,XY, t(4;15) (p14;q26). Thus, the child had trisomy for a segment of the short arm of chromosome 4 (p14----pter) and monosomy for the terminal band of the long arm of chromosome 15 (15q26). The first case of trisomy 4p was reported in 1970 by Wilson et al. Since then, there have been 46 additional reports in the medical literature. Although children with trisomy 4p share a number of features, the phenotypic manifestations of this chromosomal abnormality are variable and nonspecific, making clinical diagnosis difficult.