Effects of antidepressant medication on sexual function: a controlled study

There has been little systematic study of the types of sexual dysfunction produced by antidepressant medication or of the frequency with which this type of adverse effect occurs. The authors report results of a double-blind study in which the effects of imipramine, phenelzine, and placebo on specific aspects of sexual function were assessed in depressed outpatients before and after 6 weeks of treatment. Both active treatments were associated with a high incidence of adverse changes in sexual function and produced significantly more adverse effects on sexual function than placebo. Orgasm and ejaculation were impaired to a greater extent than erection. Adverse sexual function changes secondary to antidepressant medication occurred frequently in both men and women, although men reported a higher incidence. Antidepressant-related sexual dysfunction may be of clinical importance for medication compliance in view of current recommendations that antidepressants be administered for longer periods as maintenance therapy or for prophylaxis.     

Experience with high-dose gadolinium MR imaging in the evaluation of brain metastases.

PURPOSE: To assess the effectiveness and safety of higher doses of gadoteridol in the MR evaluation of patients with brain metastases. MATERIALS AND METHODS: Thirty-one patients with a clinical suspicion of brain metastases were studied prospectively with gadoteridol, a new, nonionic, low-osmolality contrast agent. Each patient received an initial injection of 0.1 mmol/kg and an additional dose of 0.2 mmol/kg 30 minutes later. Images were obtained before, immediately after, and 10 and 20 minutes after the initial dose. Images also were acquired immediately after the additional dose of gadoteridol. RESULTS: No adverse effects were attributed to the injection of gadoteridol. Four patients' examinations were excluded from analysis because of machine malfunction (two patients) and excessive motion artifact (two patients). Four patients had no detectable metastases. After the additional dose of gadoteridol, there was a marked qualitative improvement in lesion conspicuity and detection. The conspicuity of 80 of 81 lesions was increased in the high-dose studies, and 46 new lesions were detected in 19 of 27 patients. Quantitative image analysis demonstrated a significant increase in normalized mean lesion contrast between the initial-dose and high-dose studies (35 lesions identified in 13 patients, P less than .0001). The additional information gained by high-dose examinations contributed to a potential modification of the treatment in 10 of 27 patients. High-dose examinations increased flow-related artifact in the posterior fossa in 12 of 27 patients. CONCLUSION: Based on our preliminary results, high-dose gadolinium-enhanced MR examinations may have advantages over 0.1 mmol/kg examinations in detecting early and/or small metastases. This may be significant in the management of patients with cerebral metastases.     

Caspase inhibitors induce a switch from apoptotic to proinflammatory signaling in CD95-stimulated T lymphocytes

CD95 is a major apoptosis receptor that induces caspase activation and programmed cell death in susceptible cells. CD95-induced apoptosis can be blocked by peptidic caspase inhibitors such as benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone or Ile-Glu-Thr-Asp-fluoromethyl ketone. Here we show that stimulation of CD95 in the presence of these inhibitors induces necrosis and expression of various proinflammatory cytokines in primary T lymphocytes, such as TNF-alpha, IFN-gamma and granulocyte/macrophage colony-stimulating factor. In the absence of caspase inhibition CD95 stimulation did not result in cytokine expression, indicating that this proinflammatory signaling pathway is suppressed by active caspases. Further analysis with A3.01 T cells revealed that the proinflammatory signaling activity of CD95 was mediated by MEK/ERK, p38 and NF-kappaB signaling pathways. These findings point to a pivotal role of caspases not only as mediators of apoptosis but also as enzymes that prevent proinflammatory signaling during CD95-induced apoptosis. Moreover, our findings may be useful for the development of novel pharmacological strategies.     

Kidney Function after Treatment for Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study

BackgroundSurvivors of childhood cancer may be at increased risk for treatment-related kidney dysfunction. Although associations with acute kidney toxicity are well described, evidence informing late kidney sequelae is less robust.MethodsTo define the prevalence of and risk factors for impaired kidney function among adult survivors of childhood cancer who had been diagnosed ≥10 years earlier, we evaluated kidney function (eGFR and proteinuria). We abstracted information from medical records about exposure to chemotherapeutic agents, surgery, and radiation treatment and evaluated the latter as the percentage of the total kidney volume treated with ≥5 Gy (V5), ≥10 Gy (V10), ≥15 Gy (V15), and ≥20 Gy (V20). We also used multivariable logistic regression models to assess demographic and clinical factors associated with impaired kidney function and Elastic Net to perform model selection for outcomes of kidney function.ResultsOf the 2753 survivors, 51.3% were men, and 82.5% were non-Hispanic White. Median age at diagnosis was 7.3 years (interquartile range [IQR], 3.3–13.2), and mean age was 31.4 years (IQR, 25.8–37.8) at evaluation. Time from diagnosis was 23.2 years (IQR, 17.6–29.7). Approximately 2.1% had stages 3–5 CKD. Older age at evaluation; grade ≥2 hypertension; increasing cumulative dose of ifosfamide, cisplatin, or carboplatin; treatment ever with a calcineurin inhibitor; and volume of kidney irradiated to ≥5 or ≥10 Gy increased the odds for stages 3–5 CKD. Nephrectomy was significantly associated with stages 3–5 CKD in models for V15 or V20.ConclusionsWe found that 2.1% of our cohort of childhood cancer survivors had stages 3–5 CKD. These data may inform screening guidelines and new protocol development.     

Pediatric extracranial applications of MR angiography

Extracranial magnetic resonance angiography (MRA) was performed in 20 children to evaluate for various arterial and venous conditions. Time-of-flight and phase-contrast angiograms were constructed using a maximal-intensity-projection algorithm. The accuracy of MRA was comparable to Doppler ultrasound (n = 12) and conventional angiography (n = 3). MRA could provide an excellent mapping of patent (including collaterals) versus thrombosed vessels at sites not evaluated or inaccessible by sonography. Limitations included assessment of small and/or tortuous vessels, severely stenotic lesions, and very slow flow.     

Thallium-201 myocardial perfusion scintigrams in the evaluation of aorto-coronary saphenous bypass surgery.

The effect of aorto-coronary bypass graft surgery (CBG) upon regional myocardial perfusion (RMP) was studied in 23 patients using thallium-201 myocardial perfusing imaging after exercise. We compared the changes in RMP with the clinical status and ECG's during graded treadmill exercise (GTX) before and after CBG. After CBG, the New York Heart Association's "functional class" improved from 3.2 +/- 0.1 (mean +/- SE) to 1.2 +/- 0.2, p less than 0.005. The GTX performance of the patients was also significantly improved postoperatively as judged by the total exercise time (11.7 +/- 0.6 min postop, compared with 7.2 +/- 0.5 min preop; p less than 0.005). Postoperative improved Tl-201 scintigrams were observed in 19 patients, but in only nine patients did the perfusion distribution return to normal. Thus, Tl-201 exercise scintigrams following CBG demonstrate improved RMP in most patients. Failure of regional myocardial perfusion to improve postoperatively, however, does not preclude marked alleviation of angina and improved exercise tolerance.     

Development of a parent-proxy quality-of-life chronic cough-specific questionnaire: clinical impact vs psychometric evaluations

BACKGROUND: Chronic cough affects at least 7% of children, and the impact of this on families is significant. Although adult cough-specific quality-of-life (QOL) instruments have been shown to be a useful cough outcome measure, no suitable cough-specific QOL for parents of children with chronic cough exists. This article compares two methods of item reduction (clinical impact and psychometric) and reports on the statistical properties of both QOL instruments. METHOD: One hundred seventy children (97 boys and 73 girls; median age, 4 years; interquartile range, 3 to 7.25 years) and one of their parents participated. A preliminary 50-item parent cough-specific QOL (PC-QOL) questionnaire was developed from conversations with parents of children with chronic cough (ie, cough for > 3 weeks). Parents also completed generic QOL questionnaires (eg, Pediatric Quality of Life Inventory, version 4.0 [PedsQL4.0] and the 12-item Short Form Health Survey, version 2 [SF-12v2]). RESULTS: The clinical impact and psychometric method of item reduction resulted in 27-item and 26-item PC-QOL questionnaires, respectively, with approximately 50% of items overlapping. Internal consistency among the final items from both methods was excellent. Some evidence for concurrent and criterion validity of both methods was established as significant correlations were found between subscales of the PC-QOL questionnaire and the scales of the SF-12v2 and PedsQL4.0 scores. The PC-QOL questionnaire derived from both methods was sensitive to change following an intervention. CONCLUSION: Chronic cough significantly impacts on the QOL of both parents and children. Although the PC-QOL questionnaires derived from a clinical impact method and from a psychometric method contained different items, both versions were shown to be internally consistent and valid. Further testing is required to compare both final versions to objective and subjective cough measures.