Multiple sclerosis: management issues during pregnancy

Care of pregnant women with multiple sclerosis (MS) is challenging because of the multiple physiological changes associated with pregnancy and the need to consider the impact of any intervention on the foetus. Pregnancy is associated with clinical MS stability or improvement, while the rate of relapse rises significantly during the first three months post-partum before coming back to its level prior to pregnancy. Gestational history has no influence on long-term disability and MS does not seem to influence pregnancy or the child's health. Apart from methotrexate and cyclophosphamide, most drugs used regularly to treat MS can safely be used by pregnant women. Intravenous steroids may be used with relative safety during pregnancy. Maternal use of azathioprine is not associated with an increased risk of congenital malformations, though impaired foetal immunity, intrauterine growth retardation and prematurity are occasionally observed. Cyclosporin is not teratogenic, but may be associated with growth retardation and prematurity. Pregnancy should be avoided in women treated with methotrexate because of its known abortifacient effects and risk of causing typical malformations. Cyclophosphamide is teratogenic in animals, but population studies have not conclusively demonstrated its teratogenicity in humans. Until information is available regarding safety, glatiramer acetate, mitoxantrone, interferon-beta-1a and interferon-beta-1b should be discontinued before an anticipated pregnancy. Women with MS are no more likely to experience delivery complications than are women without MS and the mode of delivery should be decided strictly on obstetrical criteria. Spinal, epidural and general anaesthesia can all be used safely in MS patients. Young women with MS who desire children can be reassured that their infants are not at increased risk of malformations, preterm delivery, low birth weight, or infant death. The progressive nature of the disease may motivate affected women to start or complete their families as soon as possible.     

Adult polycystic disease in horseshoe kidney

A case report of kidney polycystic and horseshoe kidney coincidence in the same patient. They are two congenital associated renal diseases uncommon for urologists. The form of clinic presentation is described, the diagnostic methods used and the therapeutic management.     

Analgesia, sedation and neuromuscular block in pediatric intensive care units: present procedures and recent progress

Anxiolysis and pain control are a duty for physicians and must be treated very carefully in the Pediatric Intensive Care Units, although it is very difficult to assess them: in critically ill children sedatives and/or analgesic medications are routinely provided and titrated to obtain a satisfactory level of sedation, but different evaluation scores are needed to discriminate between light or inadequate and deep or excessive sedation, especially when the clinical examination is unavailable. It is usual to associate a benzodiazepin with an opioid, more often Midazolam and Morphine or Fentanyl; other drugs as Propofol, Clonidine and Ketamine have specific indications, brief painful procedures and weaning from long periods of sedation to avoid withdrawal. Sometimes it can be useful to add a neuromuscular blocking agent to help mechanical ventilation. Adverse sedation events are relatively frequent, associated with drug overdoses and drug interactions, particularly when 3 or more drugs are used: all class of medications and all routes of administration are involved.     

The usefulness of adenosine 99mTc tetrofosmin SPECT for the diagnosis of left anterior descending coronary artery disease in patients with chest pain and left bundle branch block

OBJECTIVES: The aim of this study was to assess the usefulness of 99mTc tetrofosmin single photon emission computed tomography (SPECT) for the diagnosis of left anterior descending (LAD) coronary artery disease in 60 subjects with left bundle branch block (LBBB) admitted for chest pain. METHODS AND RESULTS: Adenosine 99mTc tetrofosmin SPECT, transthoracic echocardiogram and coronary angiography were performed, by protocol, in 60 non-infarcted consecutive patients. The mean left ventricular ejection fraction (LVEF) was 41.6 +/- 10.8%. A significant angiographic disease of the LAD was found in 15 (25%) patients. The sensitivity and the specificity of SPECT was found to be 75% and 89%, respectively; the positive predictive value (PPV) was 70% with a negative predictive value (NPV) of 91%. During the adenosine infusion the QRS complex width reduced from 131.3 +/- 29.6 ms to 125.5 +/- 28.6 ms in the patients without LAD involvement (P = 0.008) but remained unchanged in LAD disease patients (P = 0.1). Combining SPECT information and QRS analysis the sensitivity increased to 87% with unchanged specificity, the PPV was 74% and the NPV resulted 95%. At 2-year follow-up 13 (22%) patients experienced a cardiac event. Using Kaplan-Meier analysis, an LVEF of < or = 35% was the only predictor of cardiac events (P = 0.01, log-rank 6.2). CONCLUSIONS: A quarter of patients with LBBB complaining of chest pain had LAD coronary disease. The highly negative predictive value of adenosine SPECT could help in the exclusion of LAD disease, especially when the SPECT image is combined with the QRS analysis.     

Normalization of multiple hemostatic abnormalities in uremic type 1 diabetic patients after kidney-pancreas transplantation

To evaluate the effects of kidney-pancreas transplantation on hemostatic abnormalities in uremic type 1 diabetic patients, we conducted a cross-sectional study involving 12 type 1 diabetic patients, 30 uremic type 1 diabetic patients, 27 uremic type 1 diabetic patients who had a kidney-pancreas transplant, 12 uremic type 1 diabetic patients who had a kidney-alone transplant, and 13 healthy control subjects. We evaluated platelet and clotting system. Platelets in the group of uremic type 1 diabetic patients were significantly larger than platelets in the other groups. Resting calcium levels were significantly higher in the uremic type 1 diabetic patients and uremic type 1 diabetic patients who had a kidney-alone transplant than in the type 1 diabetic patients who had a kidney-pancreas transplant and control subjects. CD41 expression was significantly reduced in platelets from the uremic type 1 diabetic patients compared with the other groups. Levels of hypercoagulability markers in the type 1 diabetic patients who had a kidney-pancreas transplant and, to a lesser extent, the uremic type 1 diabetic patients who had a kidney-alone transplant but not the uremic type 1 diabetic patients were similar to those of the control subjects. A reduction in natural anticoagulants was evident in the uremic type 1 diabetic patients, whereas near-normal values were observed in the type 1 diabetic patients who had a kidney-pancreas transplant and uremic type 1 diabetic patients who had a kidney-alone transplant. Hemostatic abnormalities were not observed in type 1 diabetic patients who had a kidney-pancreas transplant. This finding might explain the lower cardiovascular death rate observed in type 1 diabetic patients who had a kidney-pancreas transplant compared with uremic type 1 diabetic patients who had a kidney-alone transplant or uremic type 1 diabetic patients.     

Metabolic syndrome as a predictor of all-cause and cardiovascular mortality in type 2 diabetes: the Casale Monferrato Study

OBJECTIVE: The aim of this study was to assess in an 11-year survival follow-up of a population-based cohort of type 2 diabetes the predictive role of World Health Organization-defined metabolic syndrome, independent of conventional cardiovascular risk factors. RESEARCH DESIGN AND METHODS: During the follow-up (1991-2001), 1,565 patients were regularly examined with centralized measurements of HbA(1c). The independent role of the metabolic syndrome as a predictor of all-cause and cardiovascular mortality was assessed with multivariate Cox proportional hazards modeling. RESULTS: At baseline, the prevalence of the metabolic syndrome was 75.6% (95% CI 73.6-77.9). Results are based on 685 deaths (520 with the metabolic syndrome and 165 without it) in 10,890.2 person-years of observations. With respect to subjects without the metabolic syndrome, those with the metabolic syndrome had a similar hazard ratio (HR) of cardiovascular mortality after adjustment for age, sex, smoking, total cholesterol level, and coronary heart disease. In contrast, relative to subjects with diabetes only, the HR of subjects with only one component of the syndrome was 2.92 (1.16-7.33), independent of other risk factors. CONCLUSIONS: We found that 1) the prevalence of the metabolic syndrome in a population-based cohort of type 2 diabetes is high (75.6%); 2) the metabolic syndrome is not a predictor of 11-year all-cause and cardiovascular mortality; and 3) more than twofold higher cardiovascular risk, independent of conventional risk factors, is evident in diabetic subjects with only one component of the syndrome compared with those with diabetes only. Categorizing type 2 diabetic subjects as having or not having the metabolic syndrome does not provide further prediction compared with the knowledge of its single components.     

Docetaxel and prostate cancer

Prostate cancer is currently the most-frequency malignancy in men, and the second cause of death from cancer in the Western world. Once the disease has metastasized, palliative treatment is the rule. First-sine therapy consists in surgical or chemical castration, associated or not with anti-androgens. This treatment approach is active in 80% cases but failures occur within 12-18 months. When the disease becomes refractory to hormone therapy, few alternatives are available. The combination of mitoxantrone-steroids improves clinical symptoms, namely by reducing pain, but does not improve patient survival. Both docetaxel and estramustine act through microtubules and synergistic interactions have been shown between these two compounds. Recently, several studies have demonstrated the efficacy of a combination of estramustine and taxanes, and in particular docetaxel. Phase II trials using docetaxel monotherapy have demonstrated responses rates concerning PSA of 45 to 58% and objective response of 33% and 40%. Combination with estramustine increases the biochemical response rate from 45% and 74%. A randomized phase II trial revealed the superiority of this combination compared to mitoxantrone in terms of response rate and clinical benefit. The results of phase III trials are still not available, in particular as concerns survival, but the combination docetaxel-estramustine appears very promising, even though the ideal therapeutic protocol is still under evaluation.