Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured the concentrations of tissue-type plasminogen activator (t-PA) in 92 patients with chronic subdural hematoma involving 102 sites. The t-PA level in the normal plasma was 4.0 +/- 1.8 ng/mL (mean +/- SD), while that in the hematoma content of these patients was 11.2 +/- 6.2 ng/mL. Patients showing stupor (grade 3) and coma (grade 4) had higher t-PA levels than those showing headache (grade 1) and somnolence (grade 2) or psychiatric disorder (grade 5). Also, those with the layer-type hematoma on computed tomographic images had higher t-PA levels than those with any other types. The t-PA level in the draining fluid decreased after surgery. In three patients showing a gradual increase of t-PA, subdural fluid reaccumulated and the general condition remained unchanged after surgery. Overproduction of t-PA is considered to initiate intermittent hemorrhage by conversion of plasminogen to plasmin and results in persistence or enlargement of chronic subdural hematoma.
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PMID:Tissue-type plasminogen activator in the chronic subdural hematoma. 313 77

The results of a Phase II clinical trial of intrathecal recombinant tissue-type plasminogen activator for the prevention of vasospasm were reported. The subjects were 53 patients with aneurysmal subarachnoid hemorrhage (SAH), Groups 2 to 4 in Fisher's preoperative computed tomography classification and Grades II to IV in the Hunt-Kosnik classification. Twenty-four hours after surgery, tissue-type plasminogen activator (TD-2061) was intracisternally administered via a catheter (0.1, 0.2, or 0.4 mg, three times daily for 5 days). The clot-dissolving effects assessed as "effective" and "markedly effective" were virtually the same in the 0.1- and 0.2-mg groups (66.7% and 64.3%, respectively) but slightly lower (53.3%) in the 0.4-mg group, suggesting an adequate effect in the 0.1- and 0.2-mg groups. Severe angiographic vasospasm was not observed in any of three groups. No intergroup differences were noted in the incidence of symptomatic vasospasm, low density on computed tomography 1 month after SAH, and functional prognosis. Bleeding complications were noted in 4 patients (7.5%), including 1 case of SAH in the low 0.1-mg group, 2 cases of SAH in the 0.2-mg group, and 1 case of epidural hematoma in the 0.4-mg group. In overall safety rating, 3 cases with increased SAH and 1 case of epidural hematoma were assessed as "safety doubtful." Other minor side effects such as headache and hepatic dysfunction attributed to the effect of other simultaneously used drugs were assessed as "almost safe," and the rate of "almost safe" and "better" for all dose groups was about 90%, suggesting a safe dose level for all groups. These results suggest that repeated intrathecal administration of tissue-type plasminogen activator is useful for preventing vasospasm even in the low dose of 0.1 mg.
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PMID:A phase II clinical trial of recombinant human tissue-type plasminogen activator against cerebral vasospasm after aneurysmal subarachnoid hemorrhage. 780 2

Mast cells (MC) are multipotent hemopoietic effector cells producing diverse mediators like histamine, heparin, or tissue type plasminogen activator. We report a 75-year-old male patient with myelodysplastic syndrome (MDS) of recent onset (3 months' history) associated with a massive leukemic spread of immature tryptase+ MC (tentative term: myelomastocytic leukemia). The patient presented with pancytopenia, bleeding, hypofibrinogenemia, and an increased cellular tryptase level. Moreover, an excessive elevation of plasmin-antiplasmin complexes (9,200 ng/ml; normal range: 10-150), an elevated D-dimer, and an increase in thrombin-antithrombin III complexes were found. The identity of the circulating MC was confirmed by immunophenotyping (CD117/c-kit+, CD123/IL-3R alpha-, CD11b/C3biR-), biochemical analysis (cellular ratio [ng:ng] of tryptase to histamine >1), and electron microscopy. Bone marrow (bm) examination showed trilineage dysplasia (17% blasts), 30% diffusely scattered MC, and a complex karyotype. No dense, compact MC infiltrates (mastocytosis) were detectable in bm sections. Despite hyperfibrinolysis and mediator syndrome (flushing, headache), the patient received remission induction polychemotherapy (DAV) followed by two cycles of consolidation with intermediate dose ARA-C (2 x 1 g/m2/day on days 1, 3, and 5). He entered complete remission after the first chemotherapy cycle without evidence of recurring MDS. Moreover, in response to chemotherapy, the hyperfibrinolysis and mediator syndrome resolved, and the circulating c-kit+ MC disappeared. We suggest consideration of polychemotherapy as a therapeutic option in patients with high-risk MDS of recent onset, even in the case of MC lineage involvement.
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PMID:Hyperfibrinolysis in a case of myelodysplastic syndrome with leukemic spread of mast cells. 1033 14

In most cases of deep venous sinus thrombosis, systemic anticoagulation represents the initial treatment of choice for preventing propagation of a clot in the dural sinuses. In patients with deep or extensive venous sinus thrombosis, a combination of treatment modalities may be required including systemic anticoagulation, selective venous thrombolysis, and mechanical thrombectomy. In the current study the authors report on a patient who presented with the acute onset of headache, vomiting, a depressed level of consciousness, and a left hemiparesis and in whom a right middle cerebral artery (MCA) territory ischemic stroke with hemorrhagic conversion was initially diagnosed. Results of diagnostic cerebral angiography demonstrated a patent right MCA and a deep venous sinus thrombosis involving most of the dural sinuses. Despite adequate systemic heparinization, the patient's neurological condition deteriorated and direct administration of alteplase into the transverse sinus in conjunction with mechanical clot disruption using a coronary AngioJet was required. Venous flow was successfully reestablished in the deep and superficial venous sinuses by using a 0.014-in exchange wire routed from the right common femoral vein through the sinuses and out the left common femoral vein. Excellent angiographic results were obtained, and the patient had recovered completely by the 7-month follow up.
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PMID:Coronary angiojet catheterization for the management of dural venous sinus thrombosis. Technical note. 1617 70

The ratio of correct diagnosis for primary headache has always been relatively low for general practitioners due to the unacquaintance with headache guideline in Chinese primary hospitals. This study proposed a computerized headache guideline method using SAGE module and developed a decision support system for headache diagnosis, which could be expected to help general practitioners of primary hospitals improve diagnostic accuracy. 282 previously diagnosed cases from EMR were used to evaluate the diagnostic accuracy of the system, the result is: migraine 144/153 (94.1%), tension-type headache 89/100 (89.0%), cluster headache 10/11 (90.9%) and chronic daily headache 53/57(93.0%). The proposed system is in the starting phase of the implementation at the outpatient department of Neurology in Chinese PLA general hospital.
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PMID:A guideline-based decision support system for headache diagnosis. 2392 Jul 96

Lorcaserin (LOR) is a selective 5-HT2C receptor agonist that has been FDA approved as a treatment for obesity. The most frequently reported side-effects of LOR include nausea and headache, which can be dose limiting. We have previously reported that in the rat, while LOR produced unconditioned signs characteristic of nausea/malaise, the highly selective 5-HT2C agonist CP-809101 (CP) produced fewer equivalent signs. Because this may indicate a subclass of 5-HT2C agonists having better tolerability, the present studies were designed to further investigate this apparent difference. In a conditioned gaping model, a rodent test of nausea, LOR produced significantly higher gapes compared to CP consistent with it having higher emetogenic properties. Subsequent studies were designed to identify features of each drug that may account for such differences. In rats trained to discriminate CP-809101 from saline, both CP and LOR produced full generalization suggesting a similar interoceptive cue. In vitro tests of functional selectivity designed to examine signaling pathways activated by both drugs in CHO (Chinese hamster ovary) cells expressing h5-HT2C receptors failed to identify evidence for biased signaling differences between LOR and CP. Thus, both drugs showed similar profiles across PLC, PLA2, and ERK signaling pathways. In studies designed to examine pharmacokinetic differences between LOR and CP, while drug plasma levels correlated with increasing dose, CSF levels did not. CSF levels of LOR increased proportionally with dose; however CSF levels of CP plateaued from 6 to 12 mg/kg. Thus, the apparently improved tolerability of CP likely reflects a limit to CNS levels attained at relatively high doses.
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PMID:Studies To Examine Potential Tolerability Differences between the 5-HT2C Receptor Selective Agonists Lorcaserin and CP-809101. 2833 24

Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) is a syndrome also called a stroke mimic, as it can be difficult to differentiate from acute ischaemic stroke. This is a case report of a 31-year-old woman, who experienced acute neurological deficits and was treated with IV alteplase on suspicion of acute ischaemic stroke. She was later diagnosed with HaNDL. Every clinician working in acute neurology should have knowledge of this syndrome. Increased knowledge will help to diagnose and to differentiate from other potentially more harmful neurological states.
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PMID:[HaNDL is transient headache, neurological deficits and lymphocytic pleocytosis in the cerebrospinal fluid]. 3161 75

The pathophysiology of migraine is complex. Neuroimaging studies reveal functional and structural changes in the brains of migraine patients. We sought to explore regional volume differences in intracranial structures in patients with episodic and chronic migraine. Sixteen episodic migraine patients, 16 chronic migraine patients, and 24 normal controls were recruited and underwent 3.0 T MRI scanning. The volumes of 142 brain regions were calculated by an automatic volumetric algorithm and compared with clinical variables. Results demonstrated that the volumes of specific regions in the frontal and occipital lobes, and the right putamen, were increased and the volume of the fourth ventricle was decreased in the episodic migraine patients compared with controls. The volumes of the left basal forebrain, optic chiasm, and, the fourth ventricle were decreased in the chronic migraine patients, while the occipital cortex and the right putamen were larger. Compared to episodic migraine patiants, chronic migraine patients displayed larger left thalamus and smaller frontal regions. Correlation analysis showed that headache frequency was negatively correlated with the volume of the right frontal pole, right lateral orbital gyrus, and medial frontal lobes and positively correlated with the volume of the left thalamus. The sleep disturbance score was negatively correlated with the volume of the left basal forebrain. This suggests that migraine patients have structural changes in regions associated with pain processing and modulation, affective and cognitive processing, and visual perception. The remodeling of selective intracranial structures may be involved in migraine attacks. This study was approved by the Ethics Committee of Chinese PLA General Hospital (approval No. S2018-027-02) on May 31, 2018.
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PMID:Regional volume changes of the brain in migraine chronification. 3220 74

Cerebral venous sinus thrombosis (CVST) is an uncommon condition accounting for 0.5-1% of all strokes. It occurs more commonly in women, particularly in the age group of 20-40 years of age due to pregnancy and oral contraceptive use. Systemic anticoagulation is recommended as first line treatment but 10-20% of patients deteriorate despite medical treatment and require surgical or endovascular interventions. We summarize a 41-year-old female with a past medical history of acute disseminated encephalomyelitis who presented with headaches and worsening mental status. Further workup confirmed inferior sagittal sinus thrombus with intraventricular hemorrhage for which she was initiated on heparin continuous infusion. Due to worsening of clot burden and cerebral edema, a right frontal external ventricular drain was placed in addition to medical management of elevated ICP. Intravenous heparin infusion was stopped intermittently for such procedures. However, even when heparin was continued, sub-therapeutic and supra-therapeutic ranges were commonly observed, making anticoagulation management challenging. A new left-sided EVD had to be placed after increased IVH and worsening of hydrocephalus due to clotting. Due to patient's clinical worsening, a microcatheter was placed in the straight sinus and continuous alteplase via intra-sinus catheter was initiated at a rate of 1 mg/hour. This was continued for 72 hours in addition to the continuous heparin infusion. Additionally, she received intraventricular alteplase 1 mg x 3 doses for IVH. Unfortunately, she continued to deteriorate despite maximal medical therapy. She was made comfort care and expired.
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PMID:Prolonged Intra-Sinus Alteplase Infusion in Severe Case of CVST. 3292 55