Regional neurovascular coupling and cognitive performance in those with low blood pressure secondary to high-level spinal cord injury: improved by alpha-1 agonist midodrine hydrochloride

Individuals with high-level spinal cord injury (SCI) experience low blood pressure (BP) and cognitive impairments. Such dysfunction may be mediated in part by impaired neurovascular coupling (NVC) (i.e., cerebral blood flow responses to neurologic demand). Ten individuals with SCI >T6 spinal segment, and 10 age- and sex-matched controls were assessed for beat-by-beat BP, as well as middle and posterior cerebral artery blood flow velocity (MCAv, PCAv) in response to a NVC test. Tests were repeated in SCI after 10 mg midodrine (alpha₁-agonist). Verbal fluency was measured before and after midodrine in SCI, and in the control group as an index of cognitive function. At rest, mean BP was lower in SCI (70±10 versus 92±14 mm Hg; P<0.05); however, PCAv conductance was higher (0.56±0.13 versus 0.39±0.15 cm/second/mm Hg; P<0.05). Controls exhibited a 20% increase in PCAv during cognition; however, the response in SCI was completely absent (P<0.01). When BP was increased with midodrine, NVC was improved 70% in SCI, which was reflected by a 13% improved cognitive function (P<0.05). Improvements in BP were related to improved cognitive function in those with SCI (r²=0.52; P<0.05). Impaired NVC, secondary to low BP, may partially mediate reduced cognitive function in individuals with high-level SCI.     

Phenotypic characterization of white cells in white cell-reduced red cell concentrate using flow cytometry

The residual white cell (WBC) content of donated units of red cell concentrate rendered WBC-reduced by filtration through commercially available polyester filters was quantified and phenotypically analyzed. All studies were performed by flow cytometery. Quantification studies were performed with a DNA/RNA fluorophore, propidium iodide. WBC subset analyses were performed with fluorescence-labeled monoclonal antibodies directed against various cluster differentiation (CD) loci. The results indicate that the filter removes in excess of 3 log10 total WBCs from the red cell components and depletes granulocytes to or beyond the specific assay's sensitivity of 3 log10. Total T and B cells, T4 and T8 lymphocytes, and monocytes are reduced by approximately 4 log10. These analyses provide plausible explanations for the clinical success of the filter and suggest other potential applications.     

Cryptic structural lesions in refractory partial epilepsy: MR imaging and CT studies

Results of contrast material-enhanced computed tomography (CT) and T2-weighted spin-echo magnetic resonance (MR) imaging were correlated with pathologic findings in 25 patients treated surgically for refractory partial epilepsy. Of 12 lesions present, ten (83%) were detected by MR imaging and seven (58%) by CT scanning. Of nine low-grade gliomas, eight were detected by MR imaging and four by CT scanning. One posttraumatic scar and one case of temporal lobe atrophy were better demonstrated by MR imaging. A small, thrombosed arteriovenous malformation was the only lesion detected by CT scanning but not by MR imaging. No lesions were detected in 13 patients with mild gliosis and one patient with a 1.2-cm grade 1 astrocytoma. Although more sensitive than CT for detection of structural lesions in patients with refractory partial epilepsy, MR imaging resulted in a 25% false-negative diagnostic rate when a repetition time of 2,000 msec and echo time of 60 msec were used. Multi-echo imaging with at least one long echo time may be needed to increase the sensitivity of MR imaging in these patients.     

Evidence from proton magnetic resonance spectroscopy for a metabolic cascade of neuronal damage in shaken baby syndrome

OBJECTIVE: The purpose of this study was to use proton magnetic resonance spectroscopy (MRS) as a metabolic assay to describe biochemical changes during the evolution of neuronal injury in infants after shaken baby syndrome (SBS), that explain the disparity between apparent physical injury and the neurological deficit after SBS. METHODOLOGY: Three infants [6 months (A), 5 weeks (B), 7 months (C)] with SBS were examined repeatedly using localized quantitative proton MRS. Examinations were performed on days 7 and 13 (A), on days 1, 3, 5, and 12 (B), and on days 7 and 19 (C) posttrauma. Long-term follow-up examinations were performed 5 months posttrauma (A) and 4.6 months posttrauma (B). Data were compared to control data from 52 neurologically normal infants presented in a previous study. RESULTS: Spectra from parietal white matter obtained at approximately the same time after injury (5 to 7 days) showed markedly different patterns of abnormality. Infant A shows near normal levels of the neuronal marker N-acetyl aspartate, creatine, and phosphocreatine, although infant C shows absent N-acetyl aspartate, almost absent creatine and phosphocreatine, and a great excess of lactate/lipid and lipid. Analysis of the time course in infant B appears to connect these variations as markers of the severity of head injury suffered in the abuse, indicating a progression of biochemical abnormality. The principal cerebral metabolites detected by MRS that remain normal up to 24 hours fall precipitately to approximately 40% of normal within 5 to 12 days, with lactate/lipid and lipid levels more than doubling concentration between days 5 and 12. CONCLUSIONS: A strong impression is gained of MRS as a prognostic marker because infant A recovered although infants B and C remained in a state consistent with compromised neurological capacity. Loss of integrity of the proton MR spectrum appears to signal irreversible neurological damage and occurs at a time when clinical and neurological status gives no indication of long-term outcome. These results suggest the value of sequential MRS in the management of SBS.     

Retrospective study of children with hypophosphatasia with reference to dental changes

Abstract— In the present retrospective study different dental and medical parameters have been analyzed in 17 Swedish children with established hypophosphatasia (HP). It was demonstrated that the basis for the establishment of the diagnosis varied among different dentists and physicians, and that the diagnostic parameters studied among the children varied. The most reliable parameters for HP included raised levels of phosphoethanolamine in urine, and clinical and radiologic findings associated with the legs. These findings were found among the children more often than lowered values of alkaline phosphatase in serum. Histologic analysis of an extracted tooth made a valuable diagnostic complement. It is concluded that a better diagnostic uniformity is recommended. In a well functioning collaboration with well defined tasks, both dentists and physicians can contribute to a reliable diagnosis.     

Improvement in transfusion safety using a new blood unit and patient identification system as part of safe transfusion practice

A new patient and blood unit identification system designed to confirm the identity of crossmatched blood products and that of the intended recipient was evaluated. Six hundred seventy-two red cell concentrates were transfused to 312 patients. Participating hospital personnel and patients were interviewed regarding the use and benefit of this unique system, which incorporates a "lock-box" approach to the identification process. The product and procedure were accepted unanimously and enthusiastically, and three potential mistransfusions were avoided by use of the system during the limited period of observation. This type of approach to the identification process affords greater security than conventional practices and minimally burdens staff.     

Young age at first pregnancy does protect against early onset breast cancer in <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> mutation carriers

Purpose

Previous research assessing the impact of pregnancy and age at first pregnancy on breast cancer risk in BRCA1 and BRCA2 mutation carriers has produced conflicting results, with some studies showing an increased risk following early first pregnancy in contrast to the reduced risk in the general population of women. The present study addresses these inconsistencies.

Methods

Female BRCA1 and BRCA2 carriers from North West England were assessed for breast cancer incidence prior to 50 years of age comparing those with an early first full-term pregnancy (< 21 years) to those without a full-term pregnancy. Breast cancer incidence per decade from 20 years and Kaplan–Meier analyses were performed.

Results

2424 female mutation carriers (1278 BRCA1; 1146 BRCA2) developed 990 breast cancers under the age of 50 years. Women who had their first term pregnancy prior to age 21 (n = 441) had a lower cancer incidence especially between age 30–39 years. Kaplan–Meier analysis showed an odds ratio of 0.78 for BRCA1 (p = 0.005) and 0.73 for BRCA2 (p = 0.002).

Conclusions

The present study demonstrates a clear protective effect of early first pregnancy on breast cancer risk in both BRCA1 and BRCA2 mutation carriers.

     

Invasive Haemophilus influenzae type b disease in the Oxford region (1985-91)

For a seven year period (1985-91) clinical and epidemiological data were prospectively collected on children aged < 10 years with microbiologically confirmed invasive Haemophilus influenzae type b infection in the Oxford region to study the epidemiology of the disease and determine the potential impact of early primary immunisation in infants. Computer records of primary immunisations given to these cases were retrospectively analysed and, where necessary, hospital and general practitioner records were searched to determine the immunisation history. Over the seven year period, 416 cases of invasive H influenzae type b disease were reported. Widescale immunisation against H influenzae type b began in 1991 as part of a regional trial. The estimated annual incidence for invasive disease between 1985 and 1990 was 35.5 cases per 100,000 children aged less than 5 years; for H influenzae type b meningitis it was 25.1 per 100,000 children aged less than 5 years. The cumulative risks for invasive disease and meningitis by the fifth birthday were one in 560 and one in 800 respectively. The majority of disease (71%) occurred in children less than 2 years of age with the peak monthly incidences at 6 and 7 months of age. The overall mortality was 4.3% and 50% of these deaths occurred suddenly. Most (91%) of the children had received at least one primary immunisation against diphtheria, tetanus, and pertussis before H influenzae type b infection and there was only one case of parental refusal of immunisation. None had received H influenzae type b immunisation. Given a vaccine uptake of 90% by 5 months of age it is estimated that at least 82% of the H influenzae type b infections could have been prevented. Extrapolated nationally, 1150 cases of infection and 50 deaths could be prevented each year by routine primary immunisation.