Elevated adenosine deaminase activity and hereditary hemolytic anemia. Evidence for abnormal translational control of protein synthesis.

We have investigated the molecular basis of the marked elevation in erythrocyte adenosine deaminase (ADA) activity in a kindred with hereditary hemolytic anemia. Red cell ADA-specific activity was verified to be 70- to 100-fold normal levels. Western blots demonstrated a corresponding increase in erythrocyte ADA-specific immunoreactive protein. Analysis of genomic DNA revealed no evidence for amplification or major structural changes in the ADA gene. ADA-specific messenger RNA (mRNA) from proband reticulocytes was comparable in size and amount to mRNA from control reticulocytes. Translation of proband poly A+ reticulocyte mRNA in a rabbit reticulocyte lysate system and immunoprecipitation of 35S-labeled protein products with anti-ADA antibody yielded a band of approximately 42,000 apparent mol wt that was absent in translation products from control reticulocyte mRNAs. These data suggest that the increased ADA activity in red cells in this disorder results from the increased translation of an aberrant ADA mRNA.     

Basilar artery stent angioplasty for symptomatic intracranial athero-occlusive disease: complications and late midterm clinical outcomes

BACKGROUND AND PURPOSE: After an initial series of basilar artery stent angioplasty indicated a high technical success rate and minimal morbidity, subsequent reports suggested significant procedural risks. We retrospectively reviewed our experience with basilar artery stent placement to assess complications and clinical outcomes. MATERIALS AND METHODS: Ten consecutive patients with symptomatic intracranial athero-occlusive disease underwent stent placement of the basilar artery at our institution (1999-2003). We collected clinical data by chart review and determined outcomes (modified Rankin Scale [mRS]) by telephone interview. Angiographic data were analyzed by 2 blinded investigators. Clinical and angiographic variables were tested for correlation with outcome and complications using the Pearson correlation test. RESULTS: Of 10 patients (mean follow-up time, 31 months), 4 patients suffered 6 ischemic complications that were immediate in 1, early delayed (<2 weeks) in 4, and late delayed (>2 weeks) in 1. Complications included basilar artery rupture in 1 patient, access site complications in 1 patient, and other non-neurologic complications in 5. Symptomatic restenosis occurred in 1 patient. Outcomes (mRS) were excellent (0-2) in 5 patients, good (3) in 4, and poor (4-6) in 1 patient, who died. Ischemic complications were associated with lesion lumen 45 degrees (P<.05). Less favorable clinical outcomes were associated with few ischemic complications and the presence of fewer than 2 patent vertebral arteries (P<.05). CONCLUSIONS: Despite a significant incidence of ischemic and nonischemic complications after basilar artery stent placement, most patients in this small series achieved freedom from vertebrobasilar ischemia and good to excellent clinical outcomes at late midterm follow-up (12-46 months). Ischemic complications usually had an early delayed presentation and procedural risks correlated with lesion characteristics.     

Expanding the treatment window with mechanical thrombectomy in acute ischemic stroke

Introduction Acute ischemic stroke is a common disease associated with high mortality and significant long-term disability. Treatment options for acute ischemic stroke continue to evolve and include pharmaceutical and mechanical therapies. With the recent US Food and Drug Administration approval of a new device for mechanical thrombectomy, the options available for treatment of acute ischemic stroke have been expanded. Thrombolytic therapy is generally given intravenously in the first 3 h and up to 6 h via the intraarterial route for pharmacological clot disruption. The maximum time-frame for mechanical thrombectomy devices has yet to be determined.Methods A 78-year-old female presented to the emergency room with a dense right hemiparesis, leftward gaze preference and dense global aphasia. Eight hours after symptom onset, left carotid angiography confirmed a left internal carotid artery terminus occlusion. A single pass was made through the clot with an X6 Merci Retriever device.Results After a single pass, the vessel was reopened and normal flow in the left internal carotid artery was demonstrated. At the time of discharge, her neurological deficits had improved significantly. Furthermore, the final infarct area, as demonstrated on magnetic resonance imaging, was probably much smaller than it would have been if the vessel had not been recanalized.Conclusion We report the use of a new mechanical thrombectomy device 8 h after onset of ischemic symptoms, with substantial subsequent improvement in neurological outcome. In selected cases, use of the Merci Retriever can result in improved outcomes beyond the traditional 6-hwindow used for intraarterial pharmacological thrombolysis.     

Idiopathic supraclinoid and internal carotid bifurcation steno-occlusive disease in young American adults

We report a series of American adults with idiopathic steno-occlusive disease of the supraclinoid internal carotid artery and its bifurcation. We reviewed the clinical records and imaging of 18 patients, 16 women and 2 men, aged 20–53 years (mean 35 years). There were no predominating risk factors for vascular occlusive disease, such as oral contraceptive use, hypertension, diabetes mellitus, or smoking. Four patients had irregularity of their cervical internal carotid arteries in a pattern not classic but suspicious of fibromuscular dysplasia. Eleven patients met the criteria for moyamoya disease, having both bilateral disease and moyamoya collateral lenticulostriate arteries. Necropsy in one case showed intimal thickening with duplication of the internal elastic lamina involving the internal carotid artery bifurcation bilaterally. We found a marked predominance of young and middle-aged females in our American adults, but our findings do not support the association with birth-control pills previously reported. Received: 3 February 1998 Accepted: 24 December 1998     

Symptoms of ＂Heat＂ as a Pattern of Physiopathology

Objective： The guiding criteria are considered the backbone of Chinese medicine. They have previously been described as functional features （symptoms） leading to the overall assessment of human functions on the basis of a regulatory （cybernetic） model referring to the I Ging. Methods： The Heidelberg model can explain symptoms such as created by ＂heat＂ on a rational physiological level. Results ＆ Conclusion： The overall of physiological symptoms are shown as a schematic draft. The basis of ＂heat＂ is considered to be a general increase of microcirculation in the periphery. This leads to a couple of local pathophysiological consequences and sensations like 1） red tongue （the tongue is considered an embryological somatotopic system）. 2） Sensation of warmth （by increase of capillary flow）. 3） pre-inflammatory state, leading to pain modalities like ＂worse if pressed＂, as inflammations tend to be increasingly painful under pressure; 4） reddish skin, the mechanisms by which this is induced may include the release of substance P, therefore accompanied by burning sensation. Systemic pathophysiological consequences may include. Relative lack of fluid in the larger vessels, as fluid supplies peripheral capillary flow. This may lead to water saving mechanisms like thirst, dry mucosa with do, mouth, dry nose, dry lips, dry skin, and also dry stool, yellow and sparse urine.     

Distal septic emboli and fatal brachiocephalic artery mycotic pseudoaneurysm as a complication of stenting

The use of percutaneous angioplasty with subsequent intravascular metallic stent placement has gained increasing acceptance over the past decade. Infections of these stents appear to be uncommon; however, the rarity of this complication may in part be the result of a lack of availability of long-term follow-up data. A number of examples of infected cardiac and peripheral vascular stents have been reported, often with fatal consequences. Herein, we report a 74-year-old woman who underwent subclavian and brachiocephalic artery angioplasty and stent placement for symptomatic stenoses. Six months after the initial intervention, the patient returned with restenosis of the stents and underwent repeat angioplasty to restore full patency. Two weeks later, the patient was readmitted with generalized malaise and multiple erythematous, macular lesions on the right forearm and hand. Blood cultures grew Staphylococcus aureus, and a computed tomographic scan of the chest showed a large brachiocephalic artery pseudoaneurysm with surrounding hematoma. Despite prompt surgical intervention, this complication proved ultimately fatal. Infections of metallic endovascular stents are potentially life-threatening complications and must be addressed urgently, including possible surgical intervention.     

Cerebral aneurysm perforations complicating therapy with Guglielmi detachable coils: a meta-analysis

BACKGROUND AND PURPOSE: The risk of intraprocedural aneurysm perforation in patients with previously ruptured aneurysms tends to be higher than that of patients with previously unruptured aneurysms, but a statistically significant difference has not been shown. Our purpose was to define the rates of occurrence and of morbidity and mortality associated with aneurysmal perforation associated with coil embolization. METHODS: A meta-analysis of the results from 17 published retrospective reports of aneurysm perforations complicating therapy with Guglielmi detachable coils (GDCs) was performed. Rates of perforation and associated morbidity and mortality in previously ruptured and unruptured aneurysms were calculated. The mechanism of perforation was noted. RESULTS: The risk of intraprocedural perforation was significantly higher in patients with ruptured aneurysms compared with patients with unruptured aneurysms (4.1% vs 0.5%; P <.001). The combined risk of permanent neurologic disability and death associated with intraprocedural aneurysm perforation was 38% for ruptured aneurysms and 29% for unruptured aneurysms. The morbidity and mortality rates with perforations caused by coils (39%) and microcatheters (33%) were similar. The morbidity and mortality rate for microguidewire perforations was considerably lower (0%, n = 4) than the rates for coils and microcatheters, but number of cases was too low to indicate statistical significance. CONCLUSION: The risk of aneurysm perforation during GDC therapy is much higher in patients with previously ruptured aneurysms than in those with unruptured aneurysms. The morbidity and mortality rates are substantial for perforations caused by coils and microcatheters, whereas they seem to be much lower for perforations caused by microguidewires.     

One-year audit of admissions to the Intensive Care Unit of the Queen Elizabeth Central Hospital,Blantyre

The intensive care unit at Queen Elizabeth Central Hospital (QECH) has 4 beds and offers level 2 care. A retrospective audit of all admissions to the unit during 2002 was carried out. There were a total of 339 admissions giving a bed occupancy rate of 82 %. Surgical patients made up 81 % of admissions. 45% of all admissions were ventilated. Overall mortality was 38%. Ventilated patients had a mortality of 71% compared with 10% for non-ventilated. Data are also presented for mortality within the surgical and paediatric surgical admissions.