Natural course and pathogenesis of transient focal neurologic symptoms during pregnancy

OBJECTIVES: To determine the pathogenesis and course of transient focal neurologic symptoms in pregnant women and to identify prognostic variables that will enable targeted workup. DESIGN: Case-control series. SETTING: Tertiary care university hospital. PATIENTS: Pregnant patients with acute transient focal neurologic symptoms. Women with histories of migraine, recurrent thromboembolism, or cerebrovascular disease were excluded. INTERVENTIONS: Diffusion-weighted imaging (DWI), perfusion-weighted imaging, fluid-attenuated inversion recovery (FLAIR) imaging, gradient-recalled echo imaging, and magnetic resonance venography (MRV) and angiography to determine the presence of brain ischemia and venous thrombosis. Patients underwent echocardiography, duplex ultrasonography, and a battery of hypercoagulability tests and were followed up a mean of 12 months after the event. RESULTS: Twenty-eight controls and 14 patients were enrolled from 23 773 pregnancies. Mean age was 31.2 (range, 24-41) years and mean gestational age at symptom onset was 28 (range, 17-44) weeks. No controls reported transient focal neurologic symptoms, migraine aura, or headache. Presenting symptoms included dysphasia (6 patients) and hemisensory (5) and hemimotor (7) syndrome. In 4 patients, these symptoms were preceded by scintillating scotoma; in 9 patients, focal symptoms were followed by a first-ever, throbbing, migraine-like headache. Only 1 patient had evidence of frank infarction on magnetic resonance imaging (MRI); 2 patients had single, small, hyperintense bright foci on FLAIR imaging without accompanying lesions on DWI, and 11 patients had normal MRI and MRV results. Echocardiography, carotid duplex ultrasonography, and hypercoagulability results were negative in all patients. None of the patients had ischemic events and 4 (29%) developed migraines with aura headaches during follow-up. CONCLUSIONS: Focal neurologic symptoms in healthy pregnant women are frequently preceded by aural visual phenomena and can usually be attributed to a first-ever migraine attack. Cerebral ischemia is less common than migraine and can be reliably diagnosed with MRI. Extensive evaluations to assess a putative hypercoagulable state and cardiocerebrovascular pathology may not be warranted in all such patients.     

Ockham's razor or Hickam's dictum: a right atrial mass following excision of left atrial myxoma

We report a case of a 54-year-old man presenting with a rightatrial mass 7 months after undergoing a left atrial myxoma excisionsurgery. The differential diagnosis included recurrent myxomaor thrombus. The patient underwent repeat open sternotomy oncardiopulmonary bypass. Histopathological evaluation of themass revealed an organizing thrombus. This report is, to ourknowledge, the first that demonstrates right atrial thrombusshortly following excision of left atrial myxoma.     

A multicenter international study on the Spinal Cord Independence Measure, version III: Rasch psychometric validation

BACKGROUND: A third version of the Spinal Cord Independence Measure (SCIM III), made up of three subscales, was formulated following comments by experts from several countries and Rasch analysis performed on the previous version. OBJECTIVE: To examine the validity, reliability, and usefulness of SCIM III using Rasch analysis. DESIGN: Multicenter cohort study. SETTING: Thirteen spinal cord units in six countries from North America, Europe, and the Middle-East. SUBJECTS: 425 patients with spinal cord lesions (SCL). INTERVENTIONS: SCIM III assessments by professional staff members. Rasch analysis of admission scores. MAIN OUTCOME MEASURES: SCIM III subscale match between the distribution of item difficulty grades and the patient ability measurements; reliability of patient ability measures; fit of data to Rasch model requirements; unidimensionality of each subscale; hierarchical ordering of categories within items; differential item functioning across classes of patients and across countries. RESULTS: Results supported the compatibility of the SCIM subscales with the stringent Rasch requirements. Average infit mean-square indices were 0.79-1.06; statistically distinct strata of abilities were 3 to 4; most thresholds between adjacent categories were properly ordered; item hierarchy was stable across most of the clinical subgroups and across countries. In a few items, however, misfit or category threshold disordering were found. CONCLUSIONS: The scores of each SCIM III subscale appear as a reliable and useful quantitative representation of a specific construct of independence after SCL. This justifies the use of SCIM in clinical research, including cross-cultural trials. The results also suggest that there is merit in further refining the scale.     

Switching yeast from meiosis to mitosis: double-strand break repair, recombination and synaptonemal complex

Background:

When Saccharomyces cerevisiae cells that have begun meiosis are transferred to mitotic growth conditions (‘return-to-growth’, RTG), they can complete recombination at high meiotic frequencies, but undergo mitotic cell division and remain diploid. It was not known how meiotic recombination intermediates are repaired following RTG. Using molecular and cytological methods, we investigated whether the usual meiotic apparatus could repair meiotically induced DSBs during RTG, or whether other mechanisms are invoked when the developmental context changes.

Results:

Upon RTG, the rapid disappearance of meiotic features—double-strand breaks in DNA (DSBs), synaptonemal complex (SC), and SC related structures—was striking. In wild-type diploids, the repair of meiotic DSBs during RTG was quick and efficient, resulting in homologous recombination. Kinetic analysis of double-strand breakage and recombination indicated that meiotic DSB formation precedes the commitment to meiotic levels of recombination. DSBs were repaired in RTG in dmc1, but not rad51 mutants, hence repair did not occur by the usual meiotic mechanism which requires the Dmc1 gene product. In haploids, DSBs were also repaired quickly and efficiently upon RTG, showing that DSB repair did not require the presence of a homologous chromosome. In all strains examined, SC and related structures were not required for DSB repair or recombination following RTG.

Conclusions:

At least two pathways of DSB repair, which differ from the primary meiotic pathway(s), can occur during RTG: One involving interhomologue recombination, and another involving sister-chromatid exchange. DSB formation precedes commitment to recombination. SC elements appear to prevent sister chromatid exchange in meiosis.

     

MDCT to guide transcatheter aortic valve replacement and mitral valve repair

Percutaneous management of valvular heart disease is becoming a reality, with multicenter trials supporting minimally invasive procedures for both aortic and mitral valve disease. Historically, the treatment of choice has been aortic valve replacement with conventional surgery for patients with severe aortic stenosis, as the prognosis of untreated patients is poor, particularly if the patient is symptomatic. Transcatheter aortic valve replacement is now available as a minimally invasive option to treat select high-risk patients with severe aortic stenosis. At present more than 30,000 procedures have been performed worldwide, mostly confined to patients at high surgical risk. The short- and medium-term outcomes have been promising.     

Residual skin cancer after preoperative biopsy: evaluation by Mohs micrographic surgery

BACKGROUND: Some patients are referred for Mohs surgery with no or minimal clinical evidence of skin cancer at the biopsy site. OBJECTIVE: To determine the incidence of residual skin cancer at biopsy sites during Mohs micrographic surgery. METHODS: We evaluated all patients that underwent Mohs surgery for basal cell and squamous cell carcinomata in one year. The study was carried out prospectively. Debulking was done using a no. 15 blade at the clinical borders of the tumor or biopsy site. All specimens were sectioned at the middle and cut to the periphery at 20- microm intervals. RESULTS: Seven hundred and forty-one patients underwent operations. In 390 patients, a biopsy was performed prior to surgery. A total of 351 patients were biopsied as prestaged (chemocheck) during surgery. Ninety-nine (25%) of the preoperatively biopsied patients showed no residual tumor in the debulking specimen or the first layer. Of these 99 patients, 84 had basal cell carcinoma and 15 had superficial or in situ squamous carcinoma. CONCLUSIONS: In this study, preoperative biopsy for diagnosis of skin cancer of the face was curative in 25% of patients, despite pathologic diagnosis of incompletely excised tumor. However, as the majority of preoperatively biopsied patients showed residual tumor, Mohs micrographic surgery is indicated in all patients with incomplete removal of skin cancer of the head and neck.     

Volatile anesthetic preconditioning attenuates myocardial apoptosis in rabbits after regional ischemia and reperfusion via Akt signaling and modulation of Bcl-2 family proteins

We tested whether isoflurane preconditioning inhibits cardiomyocyte apoptosis and evaluated the role of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway in anesthetic preconditioning and determined whether PI3K/Akt signaling modulates the expression of pro- and antiapoptotic proteins in anesthetic preconditioning. Six-month-old New Zealand rabbits subjected to 40 min of myocardial ischemia followed by 180 min of reperfusion were assigned to the following groups: ischemia-reperfusion (I/R), isoflurane preconditioning and isoflurane plus PI3K inhibitors, wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-l-benzopyran-4-one (LY294002) (0.6 and 0.3 mg/kg i.v., respectively). Sham-operated, wortmannin+I/R, wortmannin+sham, LY294002+I/R, and LY294002+sham groups were also included. Infarct size was assessed by triphenyltetrazolium chloride staining. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and activated caspase-3 assays. Akt phosphorylation, Bax, Bcl-2, Bad, and phosphorylated Bad (phospho-Bad) expression was assessed by immunoblotting. Isoflurane preconditioning reduced infarct size compared with the I/R group: 22+/-4 versus 41+/-5% (p<0.05). The percentage of apoptotic cells decreased in the isoflurane group (3.8+/-1.2%) compared with the I/R group (12.4+/-1.6%; p<0.05). These results were also confirmed by the activated caspase-3 assay. Wortmannin and LY294002 inhibited the effects of isoflurane. Myocardial infarction increased to 44+/-3 and 45+/-2% and the percentage of apoptotic cells was 11.9+/-2.1 and 11.7+/-3.3%, respectively. Akt phosphorylation and Bcl-2 and phospho-Bad expression increased after isoflurane preconditioning, whereas Bax expression decreased. These effects were inhibited by wortmannin and LY294002. The data indicate that isoflurane preconditioning reduces infarct size and myocardial apoptosis after I/R. Activation of PI3K and modulation of the expression of pro- and antiapoptotic proteins may play a role in isoflurane-induced myocardial protection.     

Management of severe hypokalemia in hospitalized patients: a study of quality of care based on computerized databases

BACKGROUND: While administrative databases are used to assess general indicators of quality of care, a detailed audit of the process of clinical care usually requires review of hospital medical records. OBJECTIVE: To evaluate the feasibility of assessing the management of severe hypokalemia using computerized administrative and laboratory databases. METHODS: The study included all patients hospitalized in 1997 who experienced serum potassium levels of less than 3.0 mmol/L at Hadassah University Hospital, Jerusalem, Israel, a tertiary care center. Using the computerized databases, we measured the following: (1) whether a subsequent serum potassium test was performed, (2) time to the subsequent test and to normalization of the serum potassium level, (3) achievement of normokalemia, and (4) in-hospital mortality. In a random subsample of 100 patients, these measures were compared with the blinded assessment of the quality of medical management of hypokalemia, as determined from medical records, using predetermined criteria for adequate management. RESULTS: The computerized databases revealed that severe hypokalemia occurred in 866 patients (2.6% of the yearly hospitalizations): 55 patients (6.4%) had no subsequent serum potassium levels measured, and 260 (30.0%) were discharged from the hospital with a subnormal potassium level. The mean time to a subsequent test was 20 hours, and to normokalemia, 50 hours; both intervals varied by department. In-hospital mortality was 20.4%, or 10-fold that of the entire hospitalized population. A review of hospital medical records revealed inadequate clinical management of hypokalemia in 24%, which was associated with nonperformance of a subsequent test (likelihood ratio, 8.4), failure to normalize the serum potassium level (likelihood ratio, 4.2), discharge from the hospital with a subnormal potassium level (likelihood ratio, 2.1), and in-hospital death (likelihood ratio, 2.5), all of which could be determined by the computerized databases. CONCLUSIONS: The computerized laboratory database is useful in ascertaining the prevalence of severe hypokalemia and in assessing shortcomings in its management. Databases can be used to derive valid and efficient measures of the quality of the clinical management of electrolyte disorders.