Open-label trial of riluzole in generalized anxiety disorder

OBJECTIVE: There is a need to identify novel pharmacotherapies for anxiety disorders. The authors examined the safety and efficacy of riluzole, an antiglutamatergic agent, in adult outpatients with generalized anxiety disorder. METHOD: In an 8-week, open-label, fixed-dose study, 18 medically healthy patients with DSM-IV generalized anxiety disorder received treatment with riluzole (100 mg/day) following a 2-week drug-free period. The primary efficacy measure was the Hamilton Anxiety Rating Scale (HAM-A) score at endpoint. RESULTS: Twelve of the 15 patients who completed the trial responded positively to riluzole. At 8 weeks, eight of the 15 patients had HAM-A score indicating remission of their anxiety. The median time to response was 2.5 weeks. CONCLUSIONS: Riluzole appears to be an effective, well-tolerated, and rapidly acting anxiolytic medication for some patients with generalized anxiety disorder. Larger, placebo-controlled studies are indicated.     

Genetics and early disturbances of breathing control

Early disturbances in breathing control, including apneas of prematurity and apparently life-threatening events, account for some cases of sudden infant death syndrome and for a rare disorder called congenital central hypoventilation syndrome (CCHS). Data suggesting a genetic basis for CCHS have been obtained. Recently, we found heterozygous de novo mutations of the PHOX2B gene in 18 of 29 individuals with CCHS. Most mutations consisted of five to nine alanine expansions within a 20-residue polyalanine tract, probably resulting from nonhomologous recombination. Other mutations, generally inherited from one of the parents, in the coding regions of genes involved in the endothelin and RET signaling pathways and in the brain-derived-neurotrophic factor (BDNF) gene have been found in a few CCHS patients. Interestingly, all these genes are involved in the development of neural crest cells. Targeted disruption of these genes in mice has provided information on the pathophysiological mechanisms underlying CCHS. Despite the identification of these genes involved in breathing control, none of the genetically engineered mice developed to date replicate the full human CCHS respiratory phenotype. Recent insights into the genetic basis for CCHS may shed light on the genetics of other early disturbances in breathing control, such as apnea of prematurity and sudden infant death syndrome.     

Deletion of 5q31 and 7q31 in patients with stable melphalan treated multiple myeloma

Multiple myeloma represents a malignant proliferation of plasma cells derived from a single clone. It is well known that alkylating agents are capable of inducing myelodysplastic syndromes (MDS) and acute myelocytic leukemias (AML). This risk of both diseases in patients with multiple myeloma has been estimated to be 10-20% after 10 years. We aimed to evaluate the time course and the type of genetic abnormalities in melphalan-treated patients in the chronic stage of the disease. We applied fluorescence in situ hybridization methods with probes to 5q31 and 7q31 to mononuclear peripheral blood leukocytes of 18 melphalan-treated patients and compared the results to those of 8 untreated myeloma patients. We found three patients (17%) with a 5q31 deletion in their peripheral white blood cells, but no 7q31 deletion. These findings suggest that 5q- occurs before the overt development of MDS/AML and raise important concerns regarding long-term treatment of myeloma patients with alkylating agents. Also, the performance of cytogenetic evaluation should be considered before autologous transplantation. The clinical and biological implications of these findings should be evaluated in larger clinical and laboratory studies.     

Human granulocytic ehrlichiosis in Europe

Human granulocytic ehrlichiosis is an emerging infectious disease, which is transmitted by the tick Ixodes ricinus in Europe, like other diseases: Lyme disease, tick-borne encephalitis, babesiosis... This tick lives in the forest and its hematophagic activity ranges from April to October. Flu and febrile symptoms ten days after tick bite should suggest diagnosing the disease. Disease evolution is generally favorable, even if serious complications may occur. Leukopenia, thrombocytopenia, and elevated serum transaminases are common laboratory findings. Complementary assays useful for the diagnosis are: blood smear, indirect immunofluorescence, and polymerase chain reaction. Biological diagnostic criteria are more and more accurate, with the evolution of knowledge and technique. Tetracycline treatment generally leads to clinical and biological recovery. Informing physicians and occupationally exposed people should reinforce current prevention measures against tick bites.     

Relation between pain symptoms and the anatomic location of deep infiltrating endometriosis

OBJECTIVE: To investigate whether specific types of pelvic pain are correlated with the anatomic locations of deeply infiltrating endometriosis (DIE). DESIGN: Retrospective data analysis. SETTING: University tertiary referral center. PATIENT(S): Two hundred and twenty-five women with pelvic pain symptoms and DIE. INTERVENTION(S): During surgery, we recorded the anatomic locations of DIE implants and associated endometriosis. MAIN OUTCOME MEASURE(S): We studied the incidence of pelvic pain symptoms including severe dysmenorrhea, deep dyspareunia, noncyclic chronic pelvic pain, painful defecation during menstruation, urinary tract symptoms, and gastrointestinal symptoms as related to the location of DIE. RESULT(S): The frequency of severe dysmenorrhea increased with Douglas pouch adhesions and decreased with parity. The frequency of dyspareunia increased with a uterosacral ligament DIE location and decreased when it involved the bladder. The frequency of noncyclic chronic pelvic pain was higher when it involved the bowel and was lower for women who were treated for infertility. The frequency of painful defecation during menstruation was higher when DIE involved the vagina; lower urinary tract symptoms were more frequent when DIE involved the bladder and less frequent in women with a lower body mass index. Gastrointestinal symptoms were associated with bowel or vaginal DIE locations. CONCLUSION(S): The types of pelvic pain are related to the anatomic location of DIE. Knowledge of the characteristics of pelvic pain symptoms is important in the preoperative assessment of patients with suspected DIE.     

Evolution and cost trends of antihypertensive and hypolipidaemic drug treatment in France

Purpose: To assess the trends of the cost of cardiovascular disease prevention in France for period 1986–1997. Methods: MONICA population surveys conducted in two French Regions (Northern and Southwestern France). The individual costs of antihypertensive and hypolipidæmic drug treatment were established in 4765 subjects for the first (1985–1989) and the last (1995–1997) survey taking into account inflation rates and different daily posologies. Results: After correcting for inflation, minimum and maximum daily cost of antihypertensive treatment remained stable or decreased in both genders. Minimum daily cost for hypolipidæmic drugs remained stable but maximum costs increased considerably in both genders. This was further aggravated by a doubling of the number of subjects under hypolipidæmic drug treatment between both surveys. Conclusions: Individual daily cost of antihypertensive treatment has decreased whereas cost of hypolipidæmic treatment has increased during period 1985–1997. The higher number of subjects on hypolipidæmic drug therapy further increased the national expenditure for this class of drugs.     

High variability of plasma drug concentrations in dual protease inhibitor regimens

Ritonavir (RTV) strongly increases the concentrations of protease inhibitors (PIs) in plasma in patients given a combination of RTV and another PI. This pharmacological interaction is complex and poorly characterized and shows marked inter- and intraindividual variations. In addition, RTV interacts differently with saquinavir (SQV), indinavir (IDV), amprenavir (APV), and lopinavir (LPV). In this retrospective study on 542 human immunodeficiency virus-infected patients, we compared inter- and intraindividual variability of plasma PI concentrations and correlations between the C(min) (minimum concentration of drug in plasma) values for RTV and the coadministered PI C(min) values. Mean RTV C(min)s are significantly lower in patients receiving combinations containing APV or LPV than in combinations with SQV or IDV. With the most common PI dose regimens (600 mg of IDV twice a day [BID], 800 mg of SQV BID, and 400 mg of LPV BID), the interindividual C(min) variability of patients treated with a PI and RTV seemed to be lower with APV and LPV than with IDV and SQV. As regards intraindividual variability, APV also differed from the other PIs, exhibiting lower C(min) variability than with the other combinations. Significant positive correlations between RTV C(min) and boosted PI C(min) were observed with IDV, SQV, and LPV, but not with APV. Individual dose adjustments must take into account the specificity the pharmacological interaction of each RTV/PI combination and the large inter- and intraindividual variability of plasma PI levels to avoid suboptimal plasma drug concentrations which may lead to treatment failure and too high concentrations which may induce toxicity and therefore reduce patient compliance.