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Biomedical subjects

R Greenlee

Publications and source records attributed to R Greenlee.

12 recordsLinked to original sources

Treatment of dural sinus thrombosis using selective catheterization and urokinase.

Thrombosis of the cerebral dural venous sinuses, cortical draining veins, and deep cerebral veins is a rare clinical finding. Because of its low incidence and multiple etiologies, the optimum therapy for this condition will only be elucidated by a multicenter, randomized prospective study. At our institution, we favor early and aggressive management of cerebral venous sinus thrombosis with transfemoral, venous intradural infusions of the fibrinolytic agent urokinase. To date, treatment of only 13 patients using this technique has been reported in the English literature. This report adds 12 more such treated patients. Despite the presence of preinfusion infarcts in 5 patients, four of which were hemorrhagic, we incurred no major therapeutic morbidity. Functional sinus patency was achieved in 11 of 12 patients, with our only true failure occurring in an individual with symptoms of at least 2 months' duration. Good to excellent clinical outcome was achieved in 10 of 11 patients (one newborn had inadequate follow-up).

Adult

Amphetamine paired with physical therapy accelerates motor recovery after stroke. Further evidence.

BACKGROUND AND PURPOSE: In animal models of brain injury, administration of numerous pharmaceuticals is reported to facilitate functional recovery. However, only drugs that increase the release of norepinephrine have been shown to promote recovery when administered late (days to weeks) after injury. To determine whether these findings were applicable to humans, we administered the norepinephrine stimulant dextroamphetamine, paired with physical therapy, to hemiplegic stroke patients. METHODS: Ten hemiplegic patients who suffered an acute ischemic infarction were entered between days 16 and 30 after onset and randomly assigned to receive either 10 mg of dextroamphetamine or a placebo orally every fourth day for 10 sessions paired with physical therapy. The Fugl-Meyer Motor Scale was used at baseline, within each session, and for 12 months after onset as the dependent measure. Confounding medications such as alpha-adrenergic antagonists or agonists were excluded in all subjects. RESULTS: Although there were no differences between the groups at baseline (P = .599), there was a significant (P = .047) difference between the groups when the drug had been discontinued for 1 week and at the 12-month follow-up visit (P = .047). CONCLUSIONS: Administration of dextroamphetamine paired with physical therapy increased the rate and extent of motor recovery in a small group of hemiplegic stroke patients. These data support and extend previous findings of the facilitatory aspects of certain types of drugs on recovery from brain injury. The use of neuromodulation may allow the nervous system to adapt previously unused or alternative pathways to relevant external input.

Administration, Oral

Lower brain-stem origin of the median nerve N18 potential.

A patient undergoing intraoperative median nerve somatosensory evoked potential (MSEP) and brain-stem auditory evoked response (BAER) monitoring showed changes during basilar artery aneurysm clipping. There was loss of the BAER wave V, with preservation of waves I and III. Simultaneously, there also was loss of the MSEP N20 potential, with preservation of the N18, N13 and Erb's point potentials. The patient died and autopsy showed an infarct involving the whole rostro-caudal extent of the pontine tegmentum. This combination of electrophysiologic and pathologic findings may help answer questions regarding the exact generators of different MSEP potentials. In particular, it implies that medullary structures can generate the N18 potential.

Brain Stem

Developmental disorders of the lymphatic system.

Approximately 67% of human conceptuses die prenatally. Of these, a significant number involve a disorder of the lymphatic system. A small number of live-born children also exhibit congenital lymphatic malformations, including an estimated 60% of patients with Turner syndrome. These observations have prompted a search for the genetic and dysmorphologic basis and the different patterns of congenital lymphedema and associated anomalies. In this article, we attempt to summarize available pertinent information on congenital disorders of the lymphatic system and to propose a conceptual overview of lymphatic development.

Adult

Antibody-dependent cellular cytotoxicity against HIV-1 in sera of immunized chimpanzees.

After immunization of chimpanzees against HIV antigens, antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) were evaluated and compared with anti-HIV-antibody levels detected by enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers. Adult chimpanzees were immunized with different HIV-1 (LAV-BRU) antigen preparations: recombinant vaccinia virus (rVV) expressing gp160, p25 or p27nef; formalin- and beta-propiolactone-inactivated whole virus (inHIV); soluble recombinant gp160 either associated or not associated with other HIV proteins; a 25-mer peptide from the V3 region of gp120 coupled with KLH (V3-KLH). Immunization with the various rVV mixtures induced no or borderline ADCC increase above preimmune serum levels. Stronger and more sustained reactivity was elicited by inHIV. Purified HIV antigens elicited ADCC activity when the chimpanzees were naive; ADCC increased or remained at the same level when the animals had been preimmunized with rVV and/or inHIV. This type of reactivity apparently did not depend on whether gp160 alone or mixed with other proteins was used for immunization. The injection of V3-KLH resulted in only little, if any, recall ADCC response. ELISA antibody titers significantly correlated with ADCC and neutralizing antibody titers, but serum ADCC was independent of neutralizing antibody titers, an indication that the two latter serum activities are mediated by independent antibodies. Therefore, ADCC is elicited in the same manner as other antibody activities by the immunization of chimpanzees with inHIV or with purified recombinant HIV antigen preparations. The results obtained from the three chimpanzees of this series, which were subsequently challenged with infectious virus through the intravenous route, suggest that serum ADCC may be considered for vaccination purposes.

Amino Acid Sequence

Locomotor system assessment by muscle magnetic resonance imaging.

Clinical evaluation of the locomotor system has long been hampered by difficulty in assessing the morphologic and functional integrity of skeletal muscles. Diagnostic imaging represents a major advance in the diagnosis and management of patients with locomotor dysfunction through the possibility of probing beyond overlying soft tissues to identify muscle lesions, determine their extent, characterize their composition, direct invasive procedures, and monitor therapies. Magnetic resonance imaging (MRI) appears to be the most promising of available imaging methods, because of its great sensitivity to changes in muscle water distribution and fat content. Also, it can distinguish between individual deep and superficial muscles. Serial evaluations of many muscles are practical because of the safety of MRI. While the cost effectiveness in the workup of locomotor dysfunction remains to be determined, the scientific and practical clinical information now available merits further investigation by clinicians and radiologists alike. The purpose of this review is to describe the potential role of skeletal muscle MRI in evaluating the locomotor system.

Humans

Isolated symptomatic peripheral neuropathy in type 1 insulin-dependent diabetes mellitus.

Diabetic neuropathy is probably the most frequent of the chronic complications of diabetes, and is usually found in association with diabetic retinopathy and/or nephropathy. We report seven patients with long-standing insulin-dependent diabetes mellitus in whom symptomatic peripheral neuropathy was the first and only documented complication. The diagnosis of peripheral symmetrical neuropathy was based on the presence of symptoms and abnormal physical findings, confirmed with abnormal electrophysiological and/or vibratory and thermal threshold measurements. Diabetic retinopathy and nephropathy were absent. We conclude that in some type 1 insulin-dependent diabetic patients, similar to what has been reported in type 2 non-insulin-dependent diabetes, peripheral neuropathy may be the first chronic complication to become manifest. This observation provides additional evidence to suggest that each of the diabetic complications may have a different pathogenic mechanism.

Adult

Effective and fibrin-specific clot lysis by a zymogen precursor form of urokinase (pro-urokinase). A study in vitro and in two animal species.

A single-chain 55,000-mol wt form of urokinase (UK), similar to that previously isolated from urine, was purified from a transformed kidney cell culture medium and characterized; and its fibrinolytic properties were evaluated. The preparation immunoprecipitated with UK antiserum, had a low intrinsic amidolytic activity that was 0.1% of its active derivative, and resisted diisopropyl fluorophosphate treatment and inactivation by plasma inhibitors. The single-chain UK was therefore designated pro-UK. In the presence of plasmin and during clot lysis, activation by conversion to two-chain, 55,000-mol wt UK (TC-UK) was demonstrated. This did not occur during blood clotting nor on incubation with purified thrombin. Clot lysis in plasma consistently occurred in 2-5 h with 50-100 IU per ml of pro-UK, whereas comparable lysis was inconsistently achieved by 500-1,000 IU of UK. Pro-UK, in sharp contrast to UK, caused no fibrinogen degradation at fibrinolytic concentrations. In the absence of a clot, pro-UK in plasma was stable for more than 2 d. When a clot was added after incubation (37 degrees C) for 50 h, activation to full lytic activity took place. The findings in vivo were comparable but the rapid clearance of pro-UK required that it be given by a constant infusion despite its plasma stability. In rabbits, a UK-resistant species, pro-UK was significantly (P less than 0.001) more efficacious than TC-UK but neither induced significant fibrinogen degradation. In dogs, a more sensitive species, the high specificity of thrombolysis by pro-UK contrasted with the defibrinogenation and uncontrollable bleeding that accompanied thrombolysis by UK. It was concluded that clot lysis by pro-UK is more effective and specific than UK. The advantage of pro-UK is in the limitation of its activation to the site of a clot. This can be explained by an activation mechanism that is dependent, under physiological conditions, on fibrin-stabilized plasmin.

Animals

Neuroradiologic evaluation of patients with acute stroke treated with recombinant tissue plasminogen activator. The rt-PA Acute Stroke Study Group.

PURPOSE: 1) To describe the effectiveness and safety of thrombolytic therapy in patients with acute atherothrombotic and embolic stroke and 2) to study the variables of the occlusion site as seen on the angiograms, the CT signs of early ischemia, the hyperdense middle cerebral artery sign (HMCAS), and the size of the infarcts as seen on the 24-hour CT scan. METHODS: Ninety-three of 139 patients with acute stroke were treated with intravenous tissue plasminogen activator (rt-PA). The initial disease and the effects of treatment were assessed with both CT and cerebral angiography. RESULTS: Recanalization of occluded arteries occurred in 32 patients and was more frequent in distal occlusions. In general, patients displaying recanalization tended to develop small infarcts and patients with a HMCAS tended to develop large infarcts. Patients with signs of early ischemia developed large infarcts. The presence of a HMCAS was 100% fic for an occluded artery, but only 27% sensitive. Hemorrhagic transformations occurred in the distribution of the occluded arteries in 32 patients. CONCLUSIONS: Emergency cerebral angiography, which can be carried out relatively safely, adds important information about the nature and extent of the arterial occlusions, and the recanalization efficacy of fibrinolytic therapy for patients with acute stroke. Fibrinolytic therapy can be carried out with a relatively low complication rate that still needs to be correlated with the clinical benefits of the treatment. Fibrinolytic therapy in the doses utilized in this study, is more effective with distal than with proximal carotid territory occlusions.

Acute Disease