Hyperpolarized MRI - An Update and Future Perspectives.

In recent years, hyperpolarized 13C magnetic resonance spectroscopic (MRS) imaging has emerged as a complementary metabolic imaging approach. Hyperpolarization via dissolution dynamic nuclear polarization is a technique that enhances the MR signal of 13C-enriched molecules by a factor of > 104, enabling detection downstream metabolites in a variety of intracellular metabolic pathways. The aim of the present review is to provide the reader with an update on hyperpolarized 13C MRS imaging and to assess the future clinical potential of the technology. Several carbon-based probes have been used in hyperpolarized studies. However, the first and most widely used 13C-probe in clinical studies is [1-13C]pyruvate. In this probe, the enrichment of 13C is performed at the first carbon position as the only modification. Hyperpolarized [1-13C]pyruvate MRS imaging can detect intracellular production of [1-13C]lactate and 13C-bicarbonate non-invasively and in real time without the use of ionizing radiation. Thus, by probing the balance between oxidative and glycolytic metabolism, hyperpolarized [1-13C]pyruvate MRS imaging can image the Warburg effect in malignant tumors and detect the hallmarks of ischemia or viability in the myocardium. An increasing number of clinical studies have demonstrated that clinical hyperpolarized 13C MRS imaging is not only possible, but also it provides metabolic information that was previously inaccessible by non-invasive techniques. Although the technology is still in its infancy and several technical improvements are warranted, it is of paramount importance that nuclear medicine physicians gain knowledge of the possibilities and pitfalls of the technique. Hyperpolarized 13C MRS imaging may become an integrated feature in combined metabolic imaging of the future.

Epidural steroid injections in the management of cervical disc herniations with radiculopathy.

OBJECTIVES: To evaluate the efficacy and safety of cervical epidural steroid injection (CESI) in the management of cervical disc herniations with radiculopathy. METHOD: We conducted a prospective interventional study with a 1-year follow-up comprising 33 consecutive patients presenting symptoms of cervicobrachial pain; positive neurological signs; corresponding cervical disc herniation/protrusion as verified by magnetic resonance imaging (MRI); insufficient improvement on prior conservative therapy; and no claims for financial compensation. Symptoms and clinical findings were registered in validated questionnaires before the procedure. Blind midline interlaminar CESI at the level of disc herniation was administered utilizing the loss of resistance (LOR) technique. Outcome was assessed during the first 3 months by telephone interview or clinical examination and final outcome measures were obtained at 1 year using validated questionnaires. RESULTS: The study included 20 men (60%) and 13 women (40%); median age was 51 (range 30-63) years. Median duration of neck and arm pain was 72 (7-450) and 64 (5-443) days, respectively. On average, patients received 1.7 CESIs (range 1-3). Sixteen patients (49%) had only one injection. All 33 patients were potentially surgical candidates. Only two (6%) needed surgical intervention during follow-up. There was significant improvement in pain intensity and functional outcome. Intake of analgesics was significantly reduced. Eighty-two per cent would say 'yes' to receiving the same treatment again. No serious adverse events were observed. CONCLUSIONS: CESI appears to be a safe and efficient part of the treatment of patients with symptomatic cervical disc herniations and may be considered before patients are referred to surgery.

2-(Cyclohexylamino)-1-(4-cyclopentylpiperazin-1-yl)-2-methylpropan-1-one, a novel compound with neuroprotective and neurotrophic effects in vitro.

Focusing on development of novel drug candidates for the treatment of neurodegenerative diseases, we developed and synthesized a new compound, 2-(cyclohexylamino)-1-(4-cyclopentylpiperazin-1-yl)-2-methylpropan-1-one (amido-piperizine 1). The compound demonstrated robust neuroprotective properties after both glutamate excitotoxicity and peroxide induced oxidative stress in primary cortical cultures. Furthermore, amido-piperizine 1 was found to significantly induce neurite outgrowth in vitro which could suggest central reparative and regenerative potential of the compound. With these potential beneficial effects in CNS, the ability of the amido-piperizine 1 to penetrate the blood-brain barrier was tested using MDR1-MDCK cells. Amido-piperizine 1 was found not to be a P-gp substrate and to have a high blood-brain barrier penetration potential, indicating excellent availability to the CNS. Moreover, amido-piperizine 1 had a fast metabolic clearance rate in vitro, suggesting that parenteral in vivo administration seems preferable. As an attempt to elucidate a possible mechanism of action, we found that amido-piperizine 1 bound in nano-molar range to the sigma-1 receptor, which could explain the observed neuroprotective and neurotrophic properties, and with a 100-fold lower affinity to the sigma-2 receptor. These results propose that amido-piperizine 1 may hold promise as a drug candidate for the treatment of stroke/traumatic brain injury or other neurodegenerative diseases.

Physicians' beliefs and behaviour during a randomized controlled trial of episiotomy: consequences for women in their care.

OBJECTIVE: To evaluate whether physicians' beliefs concerning episiotomy are related to their use of procedures and to differential outcomes in childbirth. DESIGN: Post-hoc cohort analysis of physicians and patients involved in a randomized controlled trial of episiotomy. SETTING: Two tertiary care hospitals and one community hospital in Montreal. PARTICIPANTS: Of the 703 women at low risk of medical or obstetric problems enrolled in the trial we studied 447 women (226 primiparous and 221 multiparous) attended by 43 physicians. Subjects attended by residents or nurses were excluded. PATIENTS: intact perineum v. perineal trauma, length of labour, procedures used (instrumental delivery, oxytocin augmentation of labour, cesarean section and episiotomy), position for birth, rate of and reasons for not assigning women to a study arm, postpartum perineal pain and satisfaction with the birth experience, physicians: beliefs concerning episiotomy. RESULTS: Women attended by physicians who viewed episiotomy very unfavorably were more likely than women attended by the other physicians to have an intact perineum (23% v. 11% to 13%, p < 0.05) and to experience less perineal trauma. The first stage of labour was 2.3 to 3.5 hours shorter for women attended by physicians who viewed episiotomy favourably than for women attended by physicians who viewed episiotomy very unfavorably (p < 0.05 to < 0.01), and the former physicians were more likely to use oxytocin augmentation of labour. Physicians who viewed episiotomy more favourably failed more often than those who viewed the procedure very unfavourably to assign patients to a study arm late in labour (odds ratio [OR] 1.88, p < 0.05), both overall and because they felt that "fetal distress" or cesarean section necessitated exclusion of the subject. They used the lithotomy position for birth more often (OR 3.94 to 4.55, p < 0.001), had difficulty limiting episiotomy in the restricted-use arm of the trial and diagnosed fetal distress and perineal inadequacy more often than the comparison groups. The patients of physicians who viewed episiotomy very favourably experienced more perineal pain (p < 0.01), and of those who viewed episiotomy favourably and very favourably experienced less satisfaction with the birth experience (p < 0.01) than the patients of physicians who viewed the procedure very unfavourably. CONCLUSIONS: Physicians with favourably views of episiotomy were more likely to use techniques to expedite labour, and their patients were more likely to have perineal trauma and to be less satisfied with the birth experience. This evidence that physician beliefs can influence patient outcomes has both clinical and research implications.

Relationship of episiotomy to perineal trauma and morbidity, sexual dysfunction, and pelvic floor relaxation.

OBJECTIVE: Our purpose was to compare consequences for women of receiving versus not receiving median episiotomy early and 3 months post partum on the outcomes perineal pain, urinary and pelvic floor functioning by electromyography, and sexual functioning and to analyze the relationship between episiotomy and third- and fourth-degree tears. STUDY DESIGN: A secondary cohort analysis was performed of participants within a randomized clinical trial, analyzed by type of perineal trauma and pain, pelvic floor, and sexual consequences of such trauma, while controlling for trial arm. The study was conducted in three university or community hospitals; 356 primiparous and 341 multiparous women were studied. RESULTS: Early and 3-month-postpartum perineal pain was least for women who gave birth with an intact perineum. Spontaneous perineal tears were less painful than episiotomy. Sexual functioning was best for women with an intact perineum or perineal tears. Postpartum urinary and pelvic floor symptoms were similar in all perineal groups. At 3 months post partum those delivered with an intact perineum had the strongest pelvic floor musculature, those with episiotomy the weakest. Among primiparous women third- and fourth-degree tears were associated with median episiotomy (46/47). After forceps births were removed and 21 other variables potentially associated within such tears were controlled for, episiotomy was strongly associated with third- and fourth-degree tears (odds ratio +22.08, 95% confidence interval 2.84 to 171.53). Physicians using episiotomy at high rates also used other procedures, including cesarean section, more frequently. CONCLUSION: Perineal and pelvic floor morbidity was greatest among women receiving median episiotomy versus those remaining intact or sustaining spontaneous perineal tears. Median episiotomy was causally related to third- and fourth-degree tears. Those using episiotomy at the highest rates were more likely use other interventions as well. Episiotomy use should be restricted to specified fetal-maternal indications.

Does episiotomy prevent perineal trauma and pelvic floor relaxation?

OBJECTIVE: To compare the outcomes of the current practice of liberally or routinely employing episiotomy to prevent perineal tears and pelvic floor relaxation (control group) to a policy of restricting episiotomy use to specific fetal and maternal indications (experimental group). DESIGN: A randomized controlled trial (RCT). SETTING: Three university hospitals in Montreal. SUBJECTS: Seven hundred three low-risk women enrolled at 30 to 34 weeks of gestation were randomized late in labor to the designated trial arm, by parity, and followed up to 3 months postpartum. MAIN OUTCOME MEASURES: Antepartum and postpartum information on perineal trauma and pain, pelvic floor symptoms (urinary incontinence), and sexual activity was collected through the use of standard questionnaires; pelvic floor function was measured by electromyographic (EMG) perineometry. RESULTS: Restricting episiotomy use in primiparous women was associated with similar sutured perineal trauma to the liberal or routine approach. Multiparous women in the restricted episiotomy group more often gave birth with an intact perineum (31% compared with 19%, odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.09 to 3.16). All but one 3rd/4th-degree perineal tear was associated with median episiotomy (46 of 47 in primiparous women and 6 of 6 among multiparous women). No difference between trial groups was found in postpartum perineal pain, antepartum and 3-month postpartum EMG perineometry, and urinary and pelvic floor symptoms. CONCLUSIONS: We found no evidence that liberal or routine use of episiotomy prevents perineal trauma or pelvic floor relaxation. Virtually all severe perineal trauma was associated with median episiotomy. Restriction of episiotomy use among multiparous women resulted in significantly more intact perineums and less perineal suturing.

Miscarriage.

Newer techniques for diagnosing early pregnancy have shown that post-implantation embryo loss may be four times the accepted rate of 15%-20%. This article describes various causes of spontaneous abortion and its clinical evaluation and treatment, and proffers suggestions for answering the questions of women who have experienced this loss.