Mortality and prehospital thrombolysis for acute myocardial infarction: A meta-analysis

CONTEXT: Early administration of thrombolysis for acute myocardial infarction (AMI) may improve survival if safely and appropriately delivered. No systematic reviews that have comprehensively examined this topic exist in the literature. OBJECTIVE: To perform a meta-analysis of randomized controlled trials of prehospital vs in-hospital thrombolysis for AMI measuring in-hospital mortality. DATA SOURCES: The Cochrane search strategy was used to search MEDLINE, EMBASE, and the Science Citation Index (1982-1999); Dissertation Abstracts (1987-1999); and Current Contents (1994-1999) for the terms thrombolysis, thrombolysis therapy, prehospital, and acute myocardial infarction. In addition, text and journal article bibliographies were hand searched, the National Institutes of Health Web site was reviewed, and primary authors and thrombolytic drug manufacturers were contacted for unpublished studies. STUDY SELECTION: Randomized controlled trials of prehospital vs in-hospital thrombolysis for AMI measuring all-cause hospital mortality were included. Two authors independently reviewed 175 citations by title, abstract, or complete article. After exclusion of 30 duplicate citations, 145 studies remained, of which 6 studies and 3 follow-up studies met the inclusion criteria. DATA EXTRACTION: Independent data abstraction by 2 reviewers blinded to the journal, title, and author was confirmed by consensus. Trial quality was independently assessed by 2 other coauthors, blinded to the author, title, journal, introduction, and discussion. DATA SYNTHESIS: The results of the 6 randomized trials (n=6434) were pooled and indicated significantly decreased all-cause hospital mortality among patients treated with prehospital thrombolysis compared with in-hospital thrombolysis (odds ratio, 0.83; 95% confidence interval, 0.70-0.98). Results were similar regardless of trial quality or training and experience of the provider. Estimated (SE) time to thrombolysis was 104 (7) minutes for the prehospital group and 162 (16) minutes for the in-hospital thrombolysis group (P=.007). CONCLUSIONS: Our meta-analysis suggests that prehospital thrombolysis for AMI significantly decreases the time to thrombolysis and all-cause hospital mortality. JAMA. 2000;283:2686-2692.     

Do Multiple Measurements Employing Different Ultrasonic Techniques Improve the Accuracy of Amniotic Fluid Volume Assessment?

Summary: This investigation was undertaken to determine if the accuracy of the ultrasound assessment of abnormal amniotic fluid volume (oligohydramnios or poly-hydramnios) is improved by employing multiple sonographic amniotic fluid measurements. Four ultrasound techniques consisting of the subjective assessment (ultrasonic visualization without measurement), largest vertical pocket, amniotic fluid index and 2-diameter pocket technique were performed followed by amniocentesis and dye-dilution confirmation of amniotic fluid volume in 66 singleton pregnancies. The ultrasound accuracy to detect abnormal amniotic fluid volume ranged from 61% with the largest vertical pocket to 70% with the 2-diameter pocket procedure used separately. Receiver operator characteristic curves demonstrated that combining the 4 ultrasonic measurements did not improve the accuracy of identifying amniotic fluid volumes.     

A comparative study on potential cytogenetic fingerprints for radiation LET in human lymphocytes

PURPOSE: To carry out a comparative study on potential cytogenetic fingerprints for radiation LET in human metaphase lymphocytes. MATERIALS AND METHOD: Human lymphocytes were irradiated in vitro with 3.0 Gy 60Co gamma-rays, 0.9 Gy 3H beta-rays or 0.2 Gy 2.7 Mev neutrons. Detailed chromosome aberrations were analysed by combined FISH with pan-telomere staining and specific whole-chromosome painting (1, 2 and 4). Total chromosome translocations and insertions were also analysed by multicolour whole-chromosome painting (chromosomes 1, 2 and 4 orange, chromosomes 3, 5 and 6 green). RESULTS: Among the six proposed radiation cytogenetic fingerprints, the ratio of total simple translocations to insertions (I-ratio), showed the largest difference between low-LET 60Co gamma-ray and high-LET neutron radiation. The ratios of complete exchanges to incomplete rejoinings [S(I)-ratio] and dicentrics to interstitial deletions (H-ratio), showed a similar significant difference between low- and high-LET radiation. The ratios of centric rings to interstitial deletion (G-ratio) showed a trend of LET-related difference, but the difference was not significant in this data set. The ratios of dicentrics to centric rings (F-ratio) and apparent complete exchanges to hidden complete exchanges [S(II)-ratio], showed no difference between low- and high-LET radiation. In the 1426 radiation-induced chromosome aberrations observed after 52 h culture, evidence for sister-chromatid fusion but not telomere addition was found. CONCLUSION: Pan-telomere staining plus specific whole chromosome painting allows simultaneous and objective detection of complete or incomplete chromosome exchanges and interstitial or terminal deletions in human peripheral lymphocytes. Of the six proposed cytogenetic ratios, the I-ratio is the most effective cytogenetic fingerprint for distinguishing low-LET from high-LET radiation in human metaphase human lymphocytes.     

Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, Dioscorea polygonoides.

In this study, three steroidal sapogenins (Delta3 diosgenin, diosgenin, and pennogenin) and the phytosterols, stigmasterol and beta-sitosterol were isolated from Jamaican bitter yam, Dioscorea polygonoides. Their effects on fasting blood glucose and intestinal amylase and ATPases in streptozotocin-induced diabetic rats were studied. The diabetic rats (fed supplemented and unsupplemented diets) lost weight significantly compared to the normal group. There was a significant increase in the activity of alpha-amylase in the proximal region of the small intestinal mucosa of diabetic rats fed sapogenin extract or commercial diosgenin. However, this did not result in increased fasting blood glucose. Instead, supplementation of the diet with bitter yam sapogenin extract significantly decreased fasting blood glucose compared to the diabetic group. Supplementation of the diet with bitter yam sapogenin extract or commercial diosgenin significantly reduced Na+-K+-ATPase activity in all three regions compared to the diabetic control group. Commercial diosgenin supplementation resulted in a significant increase in Ca2+ ATPase activity in proximal region compared to the diabetic control and bitter yam sapogenin extract groups. The effect of bitter yam sapogenin extract or commercial diosgenin on intestinal Na+-K+-ATPase activity could account for their hypoglycemic properties. However, there was adverse effect on the body weight.     

Early and selective pathology of light chain neurofilament in the spinal cord and sciatic nerve of G86R mutant superoxide dismutase transgenic mice

Pathologic accumulation of neurofilament protein (NF), both within spheroids of the proximal axon and within inclusions of motor neuron somata, is a hallmark of neurodegeneration in amyotrophic lateral sclerosis (ALS). Transgenic mice that express mutations in superoxide dismutase (SOD-1), which were genetically linked to familial ALS, develop symptomatology and pathology that strongly resemble ALS and therefore provide a useful model for studying the disease. Examining NF in the G86R mutant SOD-1 transgenic mice, we previously demonstrated that phosphorylated NF accumulates in motor neuron somata of symptomatic transgenic mice. In the present study, we expand these results by examining the immunocytochemical distribution of the three subunits of NF (i.e., light, medium, and heavy chains) as well as tubulin in presymptomatic and symptomatic SOD-1 transgenic mice. Although all NF subunits, but not tubulin, accumulate along with phosphorylated NF in the spinal cord inclusions of symptomatic mice, numerous inclusions containing only light chain NF are found in the spinal cord of presymptomatic SOD-1 transgenic mice. In addition to these results in the spinal cord, intensely immunoreactive aggregates of NF-L, but not the other NF subunits or tubulin, were observed in the sciatic nerve of both symptomatic and presymptomatic mutant SOD-1 transgenic mice. These results suggest that the mechanism of NF alteration in SOD-1 transgenic mice, and also perhaps in ALS patients, originates with the disruption of NF-L, only later involving the other subunits.     

Clinical, electrophysiological, and molecular genetic studies in a new family with paramyotonia congenita

OBJECTIVES: To characterise the clinical and electrophysiological features and to determine the molecular genetic basis of pure paramyotonia congenita in a previously unreported large Irish kindred. METHODS: Clinical and neurophysiological examination was performed on three of the five affected family members. Five unaffected and three affected members of the family were available for genetic testing. Direct sequence analysis of the SCN4A gene on chromosome 17q, was performed on the proband's DNA. Restriction fragment length polymorphism (RFLP) analysis was used to screen other family members and control chromosomes for the SCN4A mutation identified. RESULTS: Each affected member had clinical and examination features consistent with pure paramyotonia congenita. Electrophysiological studies disclosed a 78% drop in compound muscle action potential (CMAP) amplitude on cooling to 20 degrees C. DNA sequence analysis identified a heterozygous point mutation G4367A in exon 24 of the SCN4A gene which segregated with paramyotonia and was absent in 200 control chromosomes. The mutation is predicted to result in a radical amino acid substitution at a highly conserved position within the voltage sensing fourth transmembrane segment of the fourth repeated domain of the sodium channel. CONCLUSIONS: The G4367A mutation is likely to be pathogenic and it associates with a pure paramyotonia phenotype. In keeping with other paramyotonia mutations in this region of the skeletal muscle sodium channel, it is predicted that this mutation will impair voltage sensing or sodium channel fast inactivation in a temperature dependent fashion. This study provides further evidence that exon 24 in SCN4A is a hot spot for paramyotonia mutations and this has implications for a DNA based diagnostic service.