Bilateral growth-related protein expression suggests a transient increase in regenerative potential following brain trauma

The potential of mature central nervous system (CNS) neurons to regenerate after injury represents a fundamental issue in neurobiology. The regional expression of proteins associated with axonal elongation, such as microtubule-associated protein 1B (MAP1B), its phosphorylated isoform (MAP1B-P), growth-associated protein 43 (GAP-43), and polysialylated neural cell-adhesion molecule (PSA-NCAM), was examined using immunohistochemistry from 24 hours to 2 months following lateral fluid percussion brain injury of moderate severity (2.4-2.6 atmospheres) in anesthetized rats. Uninjured (control) rats were subjected to anesthesia and surgery without injury or were subjected to anesthesia alone. Within the site of maximal injury, only increases in MAP1B and MAP1B-P were observed. Increased immunoreactivity was observed bilaterally for all growth-related proteins that were evaluated. By 24 hours postinjury, MAP1B and MAP1B-P increased within the cortex (P < 0.01) and the hippocampus (P < 0.001), whereas MAP1B-P also was elevated in the thalamus (P < 0.05). Within the dentate gyrus, increased immunoreactivity was observed for all proteins examined. By 48 hours postinjury, GAP-43 was elevated bilaterally within the inner molecular layers of the dentate gyrus (P < 0.005) and within the stratum lacunosum moleculare (P < 0.01), the stratum radiatum (P < 0. 005), and the stratum oriens (P < 0.05) of the hippocampus. Increased numbers of PSA-NCAM-labeled neurons were observed in the granule cell layers of the dentate gyrus from 48 hours through 2 weeks postinjury (P < 0.0005). The bilateral nature of increased expression of growth-related proteins differs from unilateral patterns of neuronal degeneration previously characterized for the lateral fluid-percussion model of brain injury. Taken together, these results suggest the existence of a temporary posttraumatic state in which the CNS may have increased regenerative potential. Enhancement of such a response may be one therapeutic strategy in treating CNS injury.     

Are obstetric risk factors and bowel symptoms associated with defaecographic and manometric abnormalities in women awaiting hysterectomy?

Abdominal hysterectomy has been shown to affect anorectal function. These studies are either population-based or have been performed retrospectively. It is not clear from the literature whether those subjects awaiting hysterectomy already have an element of pelvic floor failure and which may be related to obstetric risk factors. A complete anorectal assessment was performed in a group of women awaiting hysterectomy who did not volunteer any bowel symptoms. The patients studied were part of an ongoing study of the functional effects of abdominal hysterectomy. All had their anorectal function assessed before their respective surgery by a questionnaire (functional bowel score), Cleveland continence score, endoanal ultrasound (U/S), anal manometry, defaecatory proctogram and colonic transit. A detailed obstetric history, which included risk factors such as parity, type of delivery, duration of labour and elevated birth weight, were also recorded. Patients with previous bowel disease, bowel surgery and anal sphincter repair were excluded. There were 39 subjects with a median age of 43 years (range 31-65), respectively. Thirty-three rectocoeles and 22 intussusceptions were demonstrated. Two had poor puborectalis function, while five had cough incontinence. Two women had abnormal colonic transit. Thirteen had abnormal anal manometry. Endoanal ultrasound was normal in all patients. None of the obstetric risk factors were associated with rectocoele, intussusception or abnormal anal manometry. Low squeeze pressure was associated significantly with more bowel symptoms (P=0.03). However, rectocoele, intussusception, abnormal colonic transit, abnormal resting anal pressure and maximal tolerated volume were not statistically significantly associated with bowel symptoms. The majority of female subjects who were awaiting hysterectomy had physiological and proctographic abnormalities consistent with pelvic floor failure. Obstetric risk factors were not associated with rectocoele, intussusception, abnormal colonic transit and anal manometry in this cohort of patients. Similarly, the majority of proctographic abnormalities were not associated with bowel symptoms. However, a trend was noted associating bowel symptoms with manometric abnormalities.     

Vertebral artery dissection: warning symptoms, clinical features and prognosis in 26 patients

BACKGROUND AND OBJECTIVES: Internal carotid artery dissection has been extensively studied and well-described. Although there has been a recent increase in the number of reported cases of vertebral artery (VA) dissection, the clinical variety of presentation and the early warning symptoms have not been well-described before. Our objectives in this study include: (1) To determine the early symptoms and warning signs which may help the clinician in the early identification and treatment of patients with VA dissection. (2) To explore the variety of clinical presentation of VA dissection and its relation to prognosis. DESIGN AND SETTING: Retrospective analysis of hospital records in a tertiary academic centre for the period 1989-1999. RESULTS: Twenty-six patients were identified (13 men and 13 women). The mean age was 48. Possible precipitating factors were identified in 14 patients (53%). Sporting activity and chiropractic manipulations were the most common (15% and 11% respectively). Headache and/or neck pain was the prominent feature in 88% of patients and was a warning sign in 53%, preceding onset of stroke by up to 14 days. The most common clinical features included vertigo (57%), unilateral facial paresthesia (46%), cerebellar signs (33%), lateral medullary signs (26%) and visual field defects (15%). Bilateral VA dissection presented in six patients (24%). The most common region of dissection was the C1-C2 level (16 arteries, 51%). Intracranial VA dissection was found in eight arteries (25%). The majority of patients (83%) had favorable outcome. Poor prognosis was associated with (1) bilateral dissection; (2) intracranial VA dissection accompanied by subarachnoid hemorrhage. Only two patients reported stroke recurrence. CONCLUSIONS: Our findings show that VA dissection affects mainly middle age persons and involves both sexes equally. Headache and/or neck pain followed by vertigo or unilateral facial paresthesia is an important warning sign that may precede onset of stroke by several days. Although the majority of patients will have excellent prognosis, this was less likely in patients presenting with subarachnoid hemorrhage or bilateral VA dissection. Recurrence rate was low.     

Intravesical oxybutynin: practicalities of clinical use.

Oral anticholinergic therapy, used for the treatment of detrusor overactivity (DO), is limited by systemic side-effects and because of failure to respond. Alternative routes of administration include the intravesical route. We reviewed 11 women who were treated with intravesical oxybutynin (IVO). All had idiopathic DO, their symptoms having been unsuccessfully controlled on oral agents. Seven patients had symptomatic improvement. Six out of the eight patients that completed their voiding diaries showed a reduction in voiding frequency. Five patients found the procedure too inconvenient. Seven patients suffered chemical irritation. One patient complained of voiding difficulties. No patient reported systemic side-effects. The mean duration of treatment was 4-5 weeks; two patients continue to use IVO. IVO can be used successfully in the treatment of DO, but its use is limited due to the inconvenience related to catheterisation. With the advent of Botox and oxybutynin patches, IVO probably has a limited role.     

Which issues concerning multiple pregnancies should be addressed during psychosocial counselling?

The global rise in multiple pregnancy rates due to assisted reproductive technology has led to the development of various strategies to diminish these rates without jeopardising pregnancy. Policies at treatment centres may include the option of fetal reduction, although each centre is subject to national laws and its own guidelines. However, personal opinions and goals may also influence practice. The development of clinical decisions, therefore, is complex and subject to change. Primary prevention is the best way to reduce multiple births. For preventative psychosocial counselling, some centres employ counsellors, but if not, this becomes the physician's task. An in-depth assessment is required to define how many embryos to transfer and what risk of multiple birth is acceptable to patients. Counselling should address the following: the relationship between pregnancy rate, multiple pregnancy rate and the number of embryos transferred; benefits and risks of multiple pregnancy; and possibilities for primary and secondary prevention. Patients should voice how they feel facing these issues; which issues are worrisome; how they anticipate these possibilities; and what psychosocial support exists that could be mobilized. In summary, psychosocial counselling reinforces the partnership between couples and the assisted reproductive technology team, allowing for primary prevention and informed consent on multiple pregnancy issues.     

Factors influencing the acceleration of human factor XIa inactivation by antithrombin III

Controversy exists in the literature concerning the potentiating effect of heparin on the inactivation rate of factor XIa by antithrombin III (AT III) in both purified systems and in plasma. We have analyzed the factors that could influence this reaction and found that ionic strength of the medium, as well as the type and concentration of the heparin preparations accounted for the major discrepancies in the literature. At I = 0.43 N, a preparation of bovine lung heparin at 1 U/mL did not augment the inactivation rate of factor XIa by inhibitors in plasma or by purified AT III. However, when ionic strength was decreased, a progressive increase in the potentiating effect was observed, reaching 6.5-fold at I = 0.15 N. At saturating concentrations of heparin, which results in the formation of 100% AT III-heparin complex, (greater than ten-fold molar excess over AT III) in purified systems, all heparin preparations (porcine, bovine, low molecular weight [LMW], and high affinity) yielded an approximately 30-fold augmentation of the factor XIa inactivation rate. However, when heparin was less than saturating, we observed that various heparin preparations affected the AT III-induced inactivation of factor XIa to different degrees even though they exhibited the same inhibitory activity (1 U/mL) against thrombin. This variation resulted from differences in the number of AT III binding sites in each heparin preparation, despite a similar Kd for each. Addition of high molecular weight kininogen (HK) to AT III-heparin complexes did not enhance their ability to inhibit factor XIa, and high concentrations of HK decreased the inactivation rate. A high therapeutic dose of heparin only permits the formation of 2.5% to 16.5% of the AT III-heparin complexes that can be achieved at saturation. We observed that 1 U/mL heparin (bovine lung heparin) (high therapeutic concentration) in virtually undiluted plasma only accelerated the inactivation rate of factor XIa (in the absence of other active enzymes) less than two-fold. These new observations further support our previous conclusion that therapeutic levels of heparin have little to no influence on the inactivation rate of factor XIa in plasma.     

Entrapment of the basilar artery within a clivus fracture: Case report and literature review

A review of the literature revealed that basilar artery (BA) entrapment is a very rare (17 cases published) and severe pathological condition, which often leads to death. We report the case of a 72-year-old man who presented with a longitudinal clivus fracture associated with a basilar artery entrapment. This entrapment was responsible for a basilar artery dissection, which led to an ischemic stroke in the pons. The patient was managed with medical treatment, mainly to avoid a progression towards an ischemic stroke. It consisted of heparin therapy followed by antiplatelet therapy, which finally resulted in a successful outcome. In BA entrapment most of the patients who had a favorable outcome received antithrombotic therapy. This suggests that antithrombotic therapy might be useful in the first line treatment of post-traumatic BA entrapment.     

Application of magnetization transfer at 3.0 T in three-dimensional time-of-flight magnetic resonance angiography of the intracranial arteries

PURPOSE: To apply magnetization transfer (MT) at 3.0 T in three-dimensional time-of-flight magnetic resonance angiography of the intracranial arteries. MATERIALS AND METHODS: This study was performed on phantoms and seven volunteers to determine the effects of MT at 3.0 T. By using a modulated MT approach and an altered phase encode order, the specific absorption rate (SAR) was kept below 3 W/kg over any 8-second time period. RESULTS: For a 20-degree flip angle and 36 msec repetition time, the background suppression at 3.0 T was improved with MT by 52 +/- 5% for white matter and 40 +/- 8% for grey matter, making the distal intracranial vasculature significantly more discernible. CONCLUSIONS: MT at 3.0 T can significantly improve background suppression in 3D time-of-flight magnetic resonance angiography (MRA) of the intracranial arteries without exceeding SAR guidelines.