Systematic overview of drug interactions with antidepressant medications.

OBJECTIVE: Antidepressants are commonly used drugs with potential for numerous drug interactions. This study aims to systematically review the literature on drug interactions with antidepressants. METHODS: We searched MEDLINE (1966 to November 2003) and EMBASE (1980 to 2003), using the heading drug interactions combined with individual antidepressant names. We restricted searches to English-language articles and human studies. We screened drug interaction texts and review articles for relevant studies. We included articles reporting original human data on drug interactions with antidepressants commonly used in North America. Articles were independently evaluated by 2 reviewers on clinical effect, clinical significance, and quality of evidence. Discrepancies were resolved by consensus. RESULTS: There were 904 eligible interactions, involving 9509 patients, for a total of 598 summary interactions. Of these, 439 (73%) demonstrated an interaction, 148 (25%) had no effect, and 11 (2%) had conflicting evidence. For 510 interactions (85%), the quality of evidence was poor. It was fair for 67 (11%) interactions and good for 10 (2%) interactions. There were no interactions with excellent quality of evidence. There were 145 (24%) interactions of major clinical significance. These were predominantly hypertensive emergencies and serotonin syndrome. Most interacting drugs had central nervous system (CNS) activity. As expected, monoamine oxidase inhibitors (MAOIs) appear to be the most problematic family in terms of potential for serious drug interactions. CONCLUSIONS: Drug interactions with antidepressants are an important cause for concern, but this concern is based primarily on poor evidence. We recommend caution when combining antidepressants with other CNS drugs, particularly when coadministering MAOIs with other substances.     

Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections.

BACKGROUND AND METHODS: The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethyl-arginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections. RESULTS: During the acute phase of inflammation/infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine. Simultaneous plasma ADMA concentration was similar to that in healthy subjects while symmetric dimethyl-arginine (SDMA) levels were substantially increased and directly related with creatinine. When infection resolved, ADMA rose from 0.62 +/- 0.23 to 0.80 +/- 0.18 micromol/l (+29%, P = 0.01) while SDMA remained unmodified. ADMA changes were independent on concomitant risk factor changes and inversely related with baseline systolic and diastolic pressure. Changes in the ADMA/SDMA ratio were compatible with the hypothesis that inflammatory cytokines activate ADMA degradation. CONCLUSIONS: Resolution of acute inflammation is characterized by an increase in the plasma concentration of ADMA. The results imply that ADMA suppression may actually serve to stimulate NO synthesis or that in this situation plasma ADMA levels may not reflect the inhibitory potential of this methylarginine at the cellular level.     

Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis patients.

BACKGROUND: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. METHODS: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. RESULTS: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22). CONCLUSIONS: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.     

Labour management. Our experience.

We report a retrospective analysis of 1202 deliveries assisted by the same medical team, evaluating the clinical management of labour and the resulting type of delivery. Examination of the data revealed a gradual reduction in the number of deliveries treated pharmacologically accompanied by a reduction in the incidence of operative deliveries from 16% to 6%. Statistical analysis of the data using X2 test demonstrated a clear correlation between the administration of oxytocin and the incidence of operative deliveries (p less than or equal to 0.001). We believe that the indiscriminate use of oxytocin in labour should be avoided and that the pharmacological and operative management of labour requires precise clinical indications.     

The detection of internal mammary lymph nodal chain metastases in breast cancer using radiolabelled colloids

The authors report their studies of 39 lymphoscintigraphies performed on patients with breast cancer. They point out that interpretation of scintigraphic imaging must take into account the morphologic variations of the lymph nodes of the internal mammary chains (i.e. single central chain, single central lymph node) and the morphological difference in the symmetry of lymph nodes considered non-pathologic to avoid false positives. The authors retain that lack of visualization of a chain, conspicuous increase in size of a lymph node, asymmetry of pathologic development, or reduced uptake by one or more lymph nodes of the internal mammary chains must be interpreted as a sign of metastatic spread. The authors recommend lymphoscintigraphy as an effective technique in the screening of breast cancer patients for staging, follow-up, restaging, and planning of radiotherapy.     

Rest-injected thallium-201 redistribution and resting technetium-99m methoxyisobutylisonitrile uptake in coronary artery disease: relation to the severity of coronary artery stenosis

To compare rest-injected thallium-201 (Tl) redistribution and resting technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI) myocardial uptake in chronic coronary artery disease (CAD), 15 patients with angiographically proven CAD and left ventricular (LV) dysfunction (ejection fraction 34%±9%) were studied. All patients underwent rest-redistribution Tl and resting ^99mTc-MIBI cardiac imaging. Gated ^99mTc-MIBI images were also acquired to assess regional LV wall motion (WM). Myocardial segments (n=225) were divided into three groups on the basis of the degree of coronary artery stenosis: group 1 (total occlusion, n=82), group 2 (50%–99% of stenosis, n=84) and group 3 (<50% of stenosis, n=59). WM was significantly worse in groups 1 and 2 compared to group 3 (P<0.001), but no difference was observed between groups 1 and 2. TI and ^99mTc-MIBI uptake were significantly lower in groups 1 and 2 compared to group 3 (P < 0.001), and in group 1 compared to group 2 (P<0.001). When TI and ^99mTc-MIBI uptake were directly compared, TI uptake was higher than ^99mTc-MIBI uptake in group 1 (P<0.001), while no significant difference was observed in groups 2 and 3. Thus, both rest-injected TI redistribution and resting ^99mTc-MIBI uptake reflected the severity of coronary artery stenosis in CAD. However, in myocardial segments with total coronary occlusion T1 uptake was significantly higher than ^99mTc-MIBI uptake. Our data suggest that rest-injected Tl redistribution cardiac imaging may identify, more accurately than resting ^99mTc-MIBI imaging, the presence of viable myocardium in chronic CAD, particularly when the coronary blood flow is severely impaired.     

Isolated gastric sarcoidosis. Unique remnant of disseminated disease

Isolated granulomatous disease was identified in a gastrectomy specimen after a gastrointestinal hemorrhage in a 61-year-old white woman. She died postoperatively. No other areas of granulomatous tissue were identified at autopsy. Ten years previously, pulmonary sarcoidosis was proven on lung biopsy. Conceivable, other reported cases of unexplained "idiopathic" granulomatous disease of the stomach may represent residua of prior disseminated sarcoidosis.     

Prevalence of hereditary ataxias and spastic paraplegias in Molise,a region of Italy

Summary An epidemiological survey of hereditary ataxias and paraplegias was conducted in Molise, a region of Italy (335, 211 inhabitants on 1 January 1989). Total prevalence was 7.5 x 10^–5 inhabitants (95% confidence limits 4.8–11.1). There were 7 patients with Friedreich's disease, 5 with early onset cerebellar ataxia with retained tendon reflexes, 4 with ataxia-telangiectasia, 9 with hereditary spastic paraplegias (2 autosomal dominant and 7 autosomal recessive cases). There was no patient with autosomal dominant cerebellar ataxia.     

The potential role of lonidamine (LND) in the treatment of malignant glioma

Summary Up-to-date unsatisfactory results obtained in multimodality treatments of malignant glioma have prompted the research of new therapeutic modalities with unconventional modes of action. Lonidamine (LND) is a drug which reduces aerobic glycolytic activity in both human and experimental tumors. This effect mainly depends on the inhibition of mitochondrially-bound hexokinase (HK) which is present in large amounts in malignant cells. A Phase II study was conducted on patients with recurrent glioma; 12 patients were admitted to the study. Clinical side effects were moderate, necessitating a reduction of the dosage in only 1 case. The objective results were evaluated according to the indications of Levin. 2 responders and 3 cases of stable disease were observed out of 10 evaluable patients. The potential value of this new drug is discussed.