shukoor65/lab-rag-model huggingface dataset:
Abnormal methylation of the calcitonin gene marks progression of chronic myelogenous leukemia. The clinical aspects of disease progression in chronic myelogenous leukemia (CML) are well established, but the nature of the molecular events responsible is not known. We have previously reported a consistent pattern of novel sites of methylation in the 5' region of the calcitonin (CT) gene and other chromosome 11p loci in acute myelogenous and and lymphoid leukemias. In the present study, CT gene methylation patterns were investigated in peripheral blood from 51 patients with CML. Abnormal patterns were found in only 2 of 31 patients in chronic phase, but in 5 of 8 patients in accelerated phase, and in 11 of 12 patients in blast crisis (P less than .005). For one patient studied in blast crisis, abnormal CT gene methylation was found in the peripheral blast cells but not in the granulocytes. In two of three patients studied with CML and having normal peripheral cell patterns, abnormal patterns were found in marrow blast cells. In one patient, only partial normalization of the CT gene methylation pattern was seen after chemotherapy induction of a second chronic phase and the patient relapsed 5 months later. Our findings indicate that abnormal methylation of the 5' region of the CT gene is regularly a marker of disease progression in CML which may prove clinically useful. This abnormal methylation site is part of an imbalance in DNA methylation that may play a role in the progressive genetic instability which characterizes the advancing stages of CML.
5-Hydroxytryptamine and the pathophysiology of migraine. 5-Hydroxytryptamine (5-HT; serotonin) has long been implicated in the aetiology of migraine but the evidence remains circumstantial and certainly not definitive. Numerous papers have reviewed the background which is briefly outlined here. Although the continued belief in the primary involvement of 5-HT in the genesis of a migraine attack has recently been questioned, many antimigraine drugs undeniably interact potently with 5-HT receptors. It can be argued, however, that their modest clinical benefit results from their pharmacological effects, be they mediated through 5-HT receptors or otherwise, independently of any pathophysiological involvement of endogenous 5-HT. Nevertheless, there seems convincing evidence that central release of 5-HT by various drug mechanisms causes migraine-like headache in migraineurs. It remains to be seen whether these drugs mimic the pathological event initiating the spontaneous migraine attack. Regardless of these considerations, the focus of research on 5-HT and migraine has proved to be enormously profitable over several decades, culminating recently in the identification of a novel, potentially important, antimigraine drug for the treatment of the acute attack. This drug, sumatriptan, is a selective cranial vasoconstrictor which mediates this effect by specifically activating a particular 5-HT1 receptor subtype. Undoubtedly a precise understanding of its clinical mechanism of action, which is currently being studied by a number of groups, will lead to a better understanding of the pathogenesis of migraine. Perhaps this in turn will help in finally determining whether migraine is a vascular disease and whether or not a disturbance of 5-HT is just epiphenomenal or is truly the primary initiating pathological event.
Absorbable rings for pediatric valvuloplasty. Preliminary study. Secondary valvular stenosis is a significant risk of annular ring implantation during valvular repair in children. To avoid this problem, we have developed an absorbable prosthetic ring (APR), which induces the generation of a biologic fibroelastic ring with mitotic capability and thereby allows atrioventricular annulus growth with age. Twelve polydioxanone (PDS) biodegradable APRs were surgically implanted in immature goats. To avoid possible embolic complications from ring fragments during the absorption period, APRs were covered with an extensible sewing sheath of high-porosity polyester, allowing contact between the PDS, blood, and endocardium. Four APRs were implanted into the right atrial cavity, four in the tricuspid position, and four in the mitral position. Histological studies at 6 months showed a considerable amount of remaining PDS. At 1 year, only small residual fragments of PDS were present, surrounded by collagen and elastic fibers as well as fibroblasts with mitotic activity. This histological structure represents a new biologic fibroelastic ring, which has originated from PDS rings. Echocardiography at 12 months showed that the elasticity of APRs and fibrotic tissue allows normal systolic and diastolic valve motions. These findings, which demonstrate histological changes in native valve annuli as well as stable and elastic annuloplasty without secondary stenosis in growing animals, call for new studies involving hearts with valvular disease.
Improvement in oxygen tensions and pulmonary blood flow with intermittent distal aortic compression during normoxia, hypoxic hypoxia, and hyperoxia in neonatal piglets. BACKGROUND AND METHODS: We investigated the hypothesis that, in a newborn piglet during normoxia, hypoxia, and hyperoxia, increasing aortic pressure transiently by intermittent short-duration aortic compression would affect left-to-right shunting of blood and thus increase pulmonary artery blood flow, pulmonary arterial PO2, and aortic PO2 proximal to the point of compression. We also investigated whether a balloon atrial septostomy, by providing an open channel for communication between the right- and left-sided circulations, would further improve pulmonary blood flow and aortic PO2. Studies were performed in eight 7- to 10-day-old newborn piglets in three phases (FIO2 of 0.21, 0.12, and 1.0) before and after balloon arterial septostomy in each piglet. Blood gas measurements and hemodynamic variables were recorded before and at the end of a 30-sec period of aortic compression. RESULTS: During aortic compression, all the animals demonstrated a 50 to 70 mm Hg increase in aortic pressure proximal to the compression. Before balloon septostomy, there were 21%, 41%, and 8% increases in aortic PO2 in the room air, hypoxic, and hyperoxic phases of the experiment, respectively. There were also statistically significant increments in pulmonary blood flow and arterial pressures. After balloon septostomy, there were 35%, 25%, and 21% increments in aortic PO2 during the room air, hypoxic, and hyperoxic phases of the experiment, respectively. However, there was no statistically significant further improvement in the effects of aortic compression on PO2 with septostomy compared with those effects before septostomy. CONCLUSIONS: Our results suggest that increasing systemic arterial pressures in order to forcibly affect left-to-right shunting of blood may be potentially beneficial in the management of hypoxia in situations where low pulmonary artery blood flow may be contributing to hypoxia, e.g., in persistent pulmonary hypertension of the newborn.
Pathophysiology of ischaemia reperfusion injury: central role of the neutrophil. Ischaemia is a common clinical event leading to local and remote injury. Evidence indicates that tissue damage is largely caused by activated neutrophils which accumulate when the tissue is reperfused. If the area of ischaemic tissue is large, neutrophils also sequester in the lungs, inducing non-cardiogenic pulmonary oedema. Ischaemia reperfusion injury is initiated by production of reactive oxygen species which initially appear responsible for the generation of chemotactic activity for neutrophils. Later, once adherent to endothelium, neutrophils mediate damage by secretion of additional reactive oxygen species as well as proteolytic enzymes, in particular elastase. Therapeutic options for limiting ischaemia reperfusion injury include inhibition of oxygen radical formation, pharmacological prevention of neutrophil activation and chemotaxis, and also the use of monoclonal antibodies which prevent neutrophil-endothelial adhesion, a prerequisite for injury.
Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. Dopamine beta-hydroxylase (DBH) deficiency is a genetic disorder in which affected patients cannot synthesize norepinephrine, epinephrine, and octopamine in either the central nervous system or the peripheral autonomic neurons. Dopamine acts as a false neurotransmitter in their noradrenergic neurons. Neonates with DBH deficiency have had episodic hypothermia, hypoglycemia, and hypotension, but survivors sometimes cope relatively well until late childhood when overwhelming orthostatic hypotension profoundly limits their activities. The hypotension may be so severe that clonic seizures supervene. Most currently recognized patients are young or middle-aged adults. The diagnosis is established by the observation of severe orthostatic hypotension in a patient whose plasma norepinephrine/dopamine ratio is much less than one.
Role of surgery in multimodality therapy for gastrointestinal lymphoma. Between 1973 and 1989, 49 patients with gastrointestinal lymphomas were treated at the Virginia Mason Medical Center, Seattle, Washington, and followed in the tumor registry. The purpose of this review was to determine the influence of treatment on long-term survival of these patients. The mean age was 63 years (range: 38 to 83 years). There were 33 men and 16 women. The primary tumor sites were gastric 33 (67%), small bowel 11 (22%), and colon 5 (10%). Common signs and/or symptoms at presentation were pain (n = 38), bleeding (n = 11), and weight loss (n = 14). The diagnostic sensitivities of contrast radiography, computed tomography, and endoscopic biopsy were 76%, 89%, and 79%, respectively. Forty-eight patients were treated, and one received supportive care only. Thirty-one patients had surgical resections, 33 patients had chemotherapy, and 16 patients had radiotherapy. Most (n = 30) had multimodality treatment. Statistically significant variables affecting survival rates in patients with gastric lymphomas were lower tumor stage, younger patient age, and surgical resection.
Steatocystoma multiplex: appearance at mammography. The authors present mammographic findings in a patient with steatocystoma multiplex. Numerous oil cysts were seen in both breasts at mammography. The mammographic appearance is characteristic of, if not pathognomonic for, steatocystoma multiplex.
Alterations of platelet membrane microviscosity in essential hypertension. 1. The metabolism of blood platelets, taken as an accessible model of excitable cells, has been reported to be altered in hypertension. Most of the identified alterations concern the functions of various plasma membrane constituents. 2. A possible modification of membrane microviscosity was investigated by 1,6-diphenyl-1,3,5-hexatriene and 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene fluorescence depolarization. In order to determine whether or not the membrane structures probed by these indicators were related to platelet physiological functions, the cytosolic free Ca2+ concentration was determined in parallel. 3. At physiological temperature, the fluorescence anisotropy of 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene was decreased in untreated hypertensive patients (0.276 +/- 0.002 versus 0.288 +/- 0.002, n = 23 and 22, P less than 0.001), indicating a lowered microviscosity at the lipid-water interface of cell membrane. It correlated inversely with blood pressure (P less than 0.001) and cytosolic free Ca2+ concentration (P less than 0.030). On the contrary, 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy was observed to vary with sex but not with blood pressure. 4. These results suggest that structural membrane modifications may participate in the various functional abnormalities observed in platelets from hypertensive patients.
Bursitis of the tensor veli palatini muscle with an osteophyte on the pterygoid hamulus. Many patients with temporomandibular joint dysfunction and/or myofascial pain syndrome have numerous symptoms. In cases of multiple complaints, an attempt should be made to resolve symptoms on a step-by-step basis. In this case report, a patient was treated for only one of her numerous complaints, that is, a burning sensation on her palate when she touched the right tuberosity area with her tongue or finger.
Oxygen transport in adult respiratory distress syndrome and other acute circulatory problems: relationship of oxygen delivery and oxygen consumption. OBJECTIVE: To evaluate the evidence that oxygen consumption (VO2) is pathologically dependent on oxygen delivery (DO2). DATA SOURCES: Studies published since 1972 with their relevant bibliographies and computerized search of MEDLINE. STUDY SELECTION: All clinical papers reporting the relationship of: VO2 to DO2 in the adult respiratory distress syndrome (ARDS), sepsis, other critically ill patients, and normal individuals; cardiac output determined by measured VO2 to calculated VO2 from the arterial-mixed venous oxygen difference; blood lactate to DO2; and selected basic science studies. DATA EXTRACTION: Study quality was assessed and all pertinent data were summarized. RESULTS OF DATA EXTRACTION: Normal individuals display physiologic dependence of VO2 at very low levels of DO2 (330 mL/min.m2). Pathologic dependence of VO2 on DO2 entails two concepts: a) VO2 varies directly with DO2 over a wide range of DO2 and b) of particular import, tissue oxygen extraction is compromised. This pathologic supply dependence was initially identified in patients with ARDS; subsequently, it has been demonstrated in patients with sepsis and in a variety of other critically ill individuals. There are substantial, but not uniform, data documenting this dependence of VO2 on DO2 in ARDS. In some studies, this relationship correlates best with increased lactate concentrations. However, increased blood lactate concentrations do not accurately track other evidence of tissue hypoxia. Some researchers have attributed the finding of this supply dependency to artifact, when VO2 is determined by the arterial-mixed venous oxygen difference. However, when these methods are compared, the correlation is excellent. Others have raised the concern that appreciable changes in VO2, even over short periods of time, may result in physiologic increases in DO2. However, when "control" groups have been contemporaneously compared with patients with ARDS using the same methodology, they have not shown supply dependency. Interwoven throughout the studies reviewed is overwhelming and uniform evidence that both mixed venous oxygen tension (PVO2) and mixed venous oxygen content (CVO2) correlate poorly with cardiac output, DO2, or VO2. The inconsistencies in identifying pathologic DO2 dependency may well reflect the unknown variables that exist in patients with ARDS, perhaps better labeled, multiple organ system failure. CONCLUSIONS: Pathologic dependence of VO2 on DO2, especially the inability to increase tissue oxygen extraction, is present in most patients with ARDS and many other critically ill individuals. PVO2 and CVO2 are both unreliable indicators of cardiac output, DO2, or VO2.
Behavioral arousal in newborn infants and its association with termination of apnea. Arousal is an important protective mechanism that aids in the resolution of obstructive sleep apnea in adults and children, but its role in neonatal apnea has not been investigated. The primary aim of the present study was to determine the role of arousal in the termination of apnea in preterm infants. Videorecording was used to identify spontaneous behavioral arousal in a group of healthy full-term (n = 7) and preterm (n = 10) infants before and during polygraphic monitoring of cardiorespiratory variables and in a group of preterm infants with apnea (n = 10) during similar polygraphic monitoring. Spontaneous arousal rates (mean +/- SE) in full-term infants before and during polygraphic monitoring were 0.18 +/- 0.03 and 0.23 +/- 0.07 episodes/min, respectively. Corresponding values in nonapneic preterm infants were 0.24 +/- 0.03 and 0.24 +/- 0.02 episodes/min. In apneic preterm infants, mean spontaneous arousal rate during polygraphic recording was 0.26 +/- 0.02, but it was considerably higher during apneic sleep periods (0.59 +/- 0.17) than during nonapneic sleep periods (0.25 +/- 0.01). The frequency of occurrence of arousal was significantly higher (P less than 0.005) in long vs. short apnea, mixed vs. central apnea, and severe vs. mild apnea. Although a clear association between arousal and apneic resolution was observed in preterm infants, lack of arousal responses in a large number of apneic episodes suggests that behavioral arousal is not essential for the termination of apnea in these infants.
Superiority of granisetron to dexamethasone plus prochlorperazine in the prevention of chemotherapy-induced emesis. Trials of selective 5-hydroxytryptamine3 receptor antagonists have shown excellent antiemetic activity for chemotherapy containing cisplatin when compared with high-dose metoclopramide. There is little information about the efficacy of these new agents for chemotherapy other than for high-dose cisplatin. We performed a double-blind, randomized trial comparing a single dose of the 5-hydroxytryptamine3 receptor antagonist granisetron (BRL 43694A) as a single intravenous dose with dexamethasone plus prochlorperazine in 152 patients receiving their first course of moderately emetogenic chemotherapy (mainly doxorubicin- and cyclophosphamide-containing combinations). During the first 24 hours, there was a statistically significant advantage for the granisetron group in terms of the prevention of both nausea and emesis. There was no difference in the frequency of reported adverse events. We conclude that granisetron is more effective than dexamethasone plus prochlorperazine in patients who are receiving moderately emetogenic cytotoxic agents.
Pulsed-spray thrombolysis of arterial and bypass graft occlusions. Pulsed-spray thrombolysis is accomplished through forceful injection of a spray of highly concentrated urokinase into clot by using catheters with multiple side holes. We previously reported the immediate technical efficacy of the method in eight arterial and 10 bypass graft occlusions. We now describe the clinical efficacy of the method in a second, larger series of 23 native artery occlusions and 25 bypass graft occlusions. Transluminal angioplasty was performed after thrombolysis in 21 of the arteries and 24 of the bypass grafts. Initial thrombolysis was observed in all artery occlusions and all but one bypass graft occlusion with an average time for pulsed-spray lysis of 65 +/- 28 min in native arteries and 93 +/- 38 min in bypass grafts. Recanalization with improvement in symptoms or distal pulses after thrombolysis and angioplasty was achieved in 74% of treated arterial occlusions and 92% of treated graft occlusions. Of the 15 arteries that were recanalized and did not require adjunctive surgery, seven remained patent at 3-28 months follow-up. Nine of 23 recanalized bypass grafts required early adjunctive surgery. Of the nine synthetic and five saphenous vein grafts successfully recanalized and not requiring surgical revision, the mean patency was 4.3 +/- 3.1 months and 3.0 +/- 2.2 months, respectively. Minor complications were seen in 23% of cases. The two major complications (4%) involved one groin hematoma requiring surgery and one episode of gastrointestinal hemorrhage. We conclude that combined pulsed-spray thrombolysis and angioplasty achieve rapid and consistent arterial and graft recanalization with minimal risk. The method offers a favorable alternative to standard thrombolytic therapy of arterial occlusions. In occluded synthetic and vein bypass grafts, the technique is sometimes beneficial, either alone or combined with surgical revision.
Globus pharyngeus: long-term follow-up and prognostic factors. A prospective trial of 80 patients with globus pharyngeus is reported. An in-depth analysis of the typical history at presentation is given. The average follow-up period was 27 months (range, 21 to 42 months). The asymptomatic rate at this interval was 25%, with a further 35% reporting a significant improvement in symptoms. Three independent factors were found to influence prognosis (p less than .05). These were sex, length of history at consultation, and the presence or absence of associated throat symptoms. Male patients having a history of the globus symptom for less than 3 months and not complaining of any associated throat symptoms had the best chance of becoming asymptomatic or symptomatically improved. The presence or absence of heartburn or its treatment had no bearing on outcome.
A cohort study of stomach cancer in a high-risk American population. Demographic, smoking and dietary information was obtained from a cohort of 17,633 white American men, largely of Scandinavian and German descent, who responded to a mailed questionnaire in 1966. After 20 years of follow-up, 50% to 90% increases in mortality from stomach cancer (75 deaths) were found among foreign-born, their children, and among residents of the North Central states. An association was seen with low educational attainment and laboring or semiskilled occupations, primarily among immigrants and their children. Risk was evaluated in subjects who regularly smoked cigarettes (RR = 2.6, 95% CI = 1.1 to 5.8). A significant dose-response trend was observed, with subjects who smoked 30 or more cigarettes per day having more than a five-fold increased risk compared with those who never smoked. Elevated risks were also found for pipe smoking and smokeless tobacco use, but not for alcohol consumption. Analysis of dietary consumption of nine food groups revealed no significant associations with stomach cancer. However, total carbohydrate intake and a few individual food items (salted fish, bacon, cooked cereal, milk, and apples) were associated with increased risk. The findings of this prospective study of a high-risk population add to the limited evidence relating tobacco consumption to stomach cancer risk and suggest clues to ethnic, geographic, and dietary risk factors.
Evaluation of right ventricular regional perfusion with technetium-99m-sestamibi SPECT. To evaluate technetium-99m-sestamibi as a right ventricular perfusion imaging agent, 25 normal volunteers and 25 patients with suspected coronary disease were studied with both sestamibi and thallium-201 SPECT. All patients underwent cardiac characterization. Compared to thallium-201 images, visualization of the right ventricle was superior for sestamibi in all cases. After computer masking of the left ventricle, count profiles for each 6-mm right ventricular short-axis slice were extracted and plotted in a bull's-eye type polar map with images normalized to maximal right ventricular counts. On sestamibi right ventricular polar maps, 7 of 11 patients (64%) with right coronary stenosis had fixed or reversible inferior right ventricular defects. None of the 25 volunteers or patients without right coronary stenosis had right ventricular defects (true-negative rate = 100%). We conclude that sestamibi SPECT provides an accurate means to assess right ventricular regional perfusion, with data presentation and interpretation facilitated by the polar map display.