shukoor65/lab-rag-model huggingface dataset:
Issues, goals, and guidelines in selecting first-line drug therapy for hypertension. Modern antihypertensive therapy is enriched by an explosion in drug development that makes available increasingly specific agents whose effects have advanced our understanding of pressor mechanisms. This and other research into hypertensive mechanisms has defined the clinical, pharmacological, and endocrinologic heterogeneity of human hypertension. The sum of these developments is a greatly enhanced ability to identify curable and definable causes of hypertension and to pathophysiologically stratify the remaining cases of essential hypertension. Modern treatment can be much more specific than before. When long-term drug therapy is indicated, the regimen is more likely to achieve a primary goal for each patient, that is, the fewest possible drugs in the smallest amount and in lowest frequency. Two clinically quantifiable mechanisms for long-term arteriolar vasoconstriction can be identified within the spectrum of human hypertension. The first, renin-mediated vasoconstriction, is directly related to the plasma renin level. The second, sodium-volume-related vasoconstriction, is marked by a reciprocally subnormal renin level and involves abnormal sodium retention and calcium transport. A baseline renin-sodium profile can identify the pressure of one of these two forms of vasoconstriction and therefore is the key for the diagnosis of the two curable disorders that fully express one of the two pressor mechanisms--renovascular hypertension and primary aldosteronism. Renovascular hypertension, more common than once thought, is often cured by angioplasty. It is important to diagnose these curable forms before beginning long-term drug therapy. The renin-sodium profile, used in conjunction with serum potassium and creatinine measurements, is valuable not only in screening patients for curable forms, but also for stratifying the remainder according to the pathophysiological vasoconstrictor mechanism that underlies the hypertension. Converting enzyme inhibitors or beta-blockers are, by themselves, often effective in correcting the hypertension of high- or medium-renin patients, whereas calcium antagonists, diuretic agents, or alpha-blockers alone are most effective against the low-renin form of vasoconstriction. In the large midzone of renin values, if monotherapy fails, a rational basis for combined antirenin-antisodium volume therapies can be developed.
Animal models of fulminant hepatic failure. The six requirements for a satisfactory animal model of fulminant hepatic failure are reversibility, reproducibility, death from liver failure, a therapeutic window, a large animal model, and minimal hazard to personnel. Different models may be required to evaluate the various types of liver failure seen in man. The available models include surgical anheptic and devascularization procedures, as well as hepatotoxic drug administration using agents such as carbon tetrachloride, acetaminophen, or galactosamine. Currently combined surgical and drug models appear to provide the best model but the search for the ideal models continues.
Epipalatus: a rare intraoral teratoma. A wide range of discrete head and neck tumors are developmental, including those termed choristoma, hamartoma, dermoid cysts, teratoid tumors, and true teratomas. In classifying various teratomas, consideration is given to the embryonal layers represented within the substance of the tumor and to their level of organizational complexity. By definition, a hamartoma is a tissue mass, present at or near the time of birth, that is benign and native to the site of origin. Growth capacity of a hamartomatous process parallels that of the host organism. A choristoma, on the other hand, is a mass of tissue that is foreign to the site of discovery and is thought to result from growth to displaced primordial tissue that is histologically normal for that tissue.
Magnetic resonance imaging for detecting and treatment monitoring of orthotopic murine bladder tumor implants. We assessed the feasibility of magnetic resonance imaging (MRI) for detection and treatment monitoring of early stage orthotopic murine bladder (MBT-2) tumor implants. Thirty mice were scheduled for imaging at six, 14, 18 and 21 days after tumor implantation. Using a volume imaging coil, MRI demonstrated very early orthotopic tumors, the detection of which would otherwise have been impossible by clinical signs only. Sequential accurate assessment of tumor size was achieved by inflation of the bladders with a fixed volume of Gadolinium-DTPA contrast. The presence of established MBT-2 intravesical tumors was confirmed by gross pathology and light microscopy of the corresponding whole mount bladder sections. Histological examination of the corresponding tumor specimens revealed the presence of transitional cell bladder carcinoma which correlated very well with the topography and depth of tumor involvement as indicated on MRI. The The mice tolerated repeated MR imaging well. Early tumors at day 14 were detectable on MRI (with serial tumor growth to day 21), with no clinical signs of disease. In a subsequent study, response to intravesical tumor necrosis factor alpha (TNF-alpha) immunotherapy was monitored with serial MRI. The serial MR images from six tumor-bearing mice (three controls and three TNF-alpha treated) have been selected to illustrate the consistent findings of this study. Sequential MRI scans of TNF-alpha treated mice revealed retardation of tumor growth that correlated well with the corresponding histologic examination. The orthotopic tumor and MRI model described is ideal for preclinical evaluation of new potential intravesical chemotherapy and immunotherapy agents.
Studies on the cellular origin of neurothekeoma: clinical, light microscopic, immunohistochemical, and ultrastructural observations. The clinical, histopathologic, and immunohistochemical features of 11 cases of neurothekeoma are reported. One case was examined by electron microscopy. The mean age of the patients was 27.1 years; the study comprised eight female and three male patients. Most lesions were nondescript papules and located on the upper part of the body, seven cases of neurothekeoma on the head. Eight cases were classified as cellular neurothekeoma on the basis of a striking fascicular pattern and three cases as myxomatous neurothekeoma because of prominent myxoid stromal change. All cellular neurothekeomas failed to express S-100 protein, whereas the three myxomatous types were strongly positive for this marker. Other than vimentin, there was no significant immunoreactivity with other immunohistochemical markers. Ultrastructural study of one case of cellular neurothekeoma was inconclusive for cell type although a perineurial origin could not be excluded. On the basis of these results, we conclude that cellular neurothekeoma differs from myxomatous neurothekeoma not only by clinical and histologic findings but also by immunoreactivity with S-100 protein. These findings also suggest the existence of two distinct subtypes of neurothekeoma and possible origin of the two variants of neurothekeoma from different cell types or at least variation in phenotypic expression of a common cell type. On the other hand, it cannot be excluded that these two variants are different stages in the natural history of neurothekeoma.
Differences in prostaglandin metabolism in cultured aortic and pulmonary arterial endothelial cells exposed to acute and chronic hypoxia. In vivo, a marked difference in blood oxygen tension exists between the pulmonary artery and the aorta. Responses of vascular endothelial cells from these vessels to changes in ambient oxygen might be influenced by the oxygen tension to which they are continuously exposed in vivo or by their anatomic site. To explore this hypothesis, we initially studied the production of the cyclooxygenase metabolites prostacyclin and thromboxane in bovine aortic and main pulmonary arterial endothelial cells grown in 21% O2 and exposed to different degrees of acute hypoxia over a wide range of times. We found that short-term hypoxia (3% or 0% O2) rapidly and transiently activates the cyclooxygenase pathway in both cell types, with a more rapid response in bovine aortic endothelial cells. To determine whether culture in an oxygen tension similar to that to which main pulmonary arterial endothelial cells are exposed in vivo alters this response, we evaluated these cyclooxygenase metabolites in bovine aortic and main pulmonary arterial endothelial cells cultured long-term in 3% O2, both at baseline and after exposure to acute anoxia (0% O2). In both cell types, we found a decrease in prostacyclin and thromboxane synthesis at baseline and evidence of an increase in the Vmax of thromboxane synthetase following stimulation with exogenous arachidonic acid. In chronically hypoxic cells exposed to acute anoxia, there were marked differences in enzyme activity compared with that in endothelial cells maintained in 21% O2 with differences depending on the origin of the endothelial cells. In bovine aortic endothelial cells, production of neither cyclooxygenase metabolite increased; in bovine main pulmonary arterial endothelial cells, only thromboxane production increased, suggesting isolated activation of the cyclooxygenase-thromboxane synthetase pathway. These studies demonstrate that acute and chronic hypoxia have profound effects on endothelial cell cyclooxygenase metabolism and that these effects depend on the duration and degree of the hypoxic exposure and the vascular bed from which the endothelial cells are derived.
Mechanism of analgesia induced by hypnosis and acupuncture: is there a difference? Hypnosis and acupuncture can alleviate experimentally induced pain but the mechanism of analgesia remains unclear for both techniques. Experimental pain was induced by cold pressor test (CPT) in 8 male volunteers. Analgesic effect of hypnosis (HA) and acupuncture (AA) was assessed before and after double-blind administration of placebo or naloxone, in a prospective, cross-over study. We found that pain intensity was significantly lower with HA as compared with AA, both with naloxone (P less than 0.001) and placebo (P less than 0.001). Within HA or AA groups, pain scores did not differ significantly when naloxone or placebo was administered. During AA, however, pain scores were similar to control values when naloxone was given (P = 0.05) but decreased significantly with placebo (P less than 0.002). Analog scales for pain intensity and pain relief showed a good correlation (r = 0.94). Plasma levels of beta-endorphins did not change significantly in any combination. Heart rate, peripheral arterial blood pressure and skin conductance were very insensitive indices to assess pain intensity or relief, as well as intensity of acupuncture stimulation or depth of hypnotic trance. We conclude: (1) HA and AA can significantly reduce pain from CPT, and HA is more effective than AA: (2) HA and AA are not primarily mediated by the opiate endorphin system; and (3) plasmatic levels of beta-endorphins are not significantly affected by either HA or AA nor by naloxone or placebo administration.
Mechanisms of asphyxial brain damage, and possible pharmacologic interventions, in the fetus. An examination of the cellular and molecular mechanisms of neuronal cell damage may lead to the design of pharmacologic interventions during presumed or actual fetal asphyxia. Hypoxia-ischemia in its severest form results in insufficient adenosine 5'-triphosphate production. The most important effect of this is failure of adenosine 5'-triphosphate-dependent membrane functions, which maintain ionic homeostasis, that is, ionic pumping. There is K+ efflux and Na+ influx across the cell membrane, depolarization of the cell membrane, opening of the voltage-dependent calcium channels, and entrance of Ca++ into the cell. Cytosolic Ca++ is also increased by Ca++ efflux from the mitochondria and the sarcoplasmic reticulum. Ca++ is a toxin in high cytosolic concentrations; it activates phospholipases A and C, which cause membrane breakdown and release of free fatty acids, including arachidonic acid. The membrane is damaged, lysis occurs, and the neuron dies. High cytosolic Ca++ also causes release of excitatory amino acids (especially glutamate), which overwhelm the suppressant neurotransmitters, causing seizures, increased metabolism, and aggravation of the insufficient adenosine 5'-triphosphate availability. Thromboxane A2 is generated from arachidonic acid, increasing smooth muscle tone and thereby worsening the ischemia. Cyclooxygenase activity also results in formation of oxygen-free radicals that contribute to cell membrane damage, lysis, and death. Possibilities for pharmacologic interventions include (1) calcium channel blockers and antagonists, (2) excitatory neurotransmitter blockers, (3) oxygen-free radical scavengers (e.g., superoxide dismutase), (4) cyclooxygenase or prostaglandin synthesis inhibitors, and (5) seizure suppressants (e.g., phenobarbital). Some of these treatments have been shown experimentally to limit neuronal death in the adult and fetus, and after more investigative work they may be applicable to clinical practice.
The expression of CD22 (Leu 14) and CD11c (LeuM5) in chronic lymphoproliferative disorders using two-color flow cytometric analysis. The monoclonal antibodies (MoAbs) CD22 and CD11c recognize B-lymphocyte- and monocyte-associated antigens, respectively. Reports indicate that when these two MoAbs co-express, they represent a unique marker for hairy cell leukemia (HCL) although neither is specific for that disease. The authors evaluated the expression and diagnostic utility of CD22 and CD11C in specimens from 26 normal subjects, 29 patients, with various nonlymphoproliferative disorders (NLPDs), and 75 patients with different types of chronic lymphoproliferative disorders (CLDs) using two-color flow cytometric analysis of peripheral blood lymphocytes. Lymphocytes co-expressed CD22 and CD11c in less than or equal to 3% of the normal subjects and in less than or equal to 6% of the patients with NLPDs. These markers were expressed in greater than 10% of the lymphocytes of 46% (32/69) of the patients with B-cell CLDs: B-cell chronic-lymphocytic leukemia, 9/41; B-cell non-Hodgkin's lymphoma, 8/14; HCL, 11/11; B-cell lymphoproliferative disorder (NOS), 1/2; and B-cell prolymphocytic leukemia, 1/1. None (0/6) of the lymphocytes of patients with T-cell CLDs expressed greater than 10% CD22-positive (CD22+) or CD11c-positive (CD11c+) cells. The HCL cases demonstrated a unique CD22+CD11c+ fluorescence histogram pattern, distinct from other lymphoproliferative disorders, that was characterized by uniformly intense CD11c and CD22 fluorescence. Differences in the expression of the CD22+CD11C- and CD22+CD11C+ phenotypes between diagnostic groups were found, most notable was a paucity of CD22+CD11c+ cells in lymphocytes of patients with HCL. CD22 also had more variable expression than CD19 and HLA-DR in the cases of B-cell CLD. This study demonstrates that the CD22+CD11c+ phenotype is not unique to HCL but is a consistent feature of that disorder and that the immunofluorescence pattern of co-expression in HCL is diagnostically useful.
Benign recurrence of a pilocytic cerebellar astrocytoma 36 years after radical removal: case report. A benign recurrence of a cerebellar juvenile astrocytoma was found in a 52-year-old woman 36 years after the initial radical removal, which was performed when she was 16 years of age. To our knowledge, this is the third detailed case report of the late benign recurrence of cerebellar astrocytoma after total removal. The problem of recurrence of cerebellar astrocytoma is reviewed.
Recurrent mild abruptio placentae occurring immediately after repeated electroconvulsive therapy in pregnancy. We present a case in which electroconvulsive therapy was performed repeatedly in pregnancy because of severe depression with psychotic features and failure of chemical treatment. Each electroconvulsive treatment was immediately followed by uterine contractions and active uterine bleeding, possibly representing recurrent abruptio placentae occurring in association with the treatment. Transient acute episodes of maternal hypertension between 180/90 and 190/100 mm Hg, documented within minutes after application of each electroconvulsive treatment, might explain the abruptio placentae manifested by active uterine bleeding and uterine hyperstimulation.
Interleukin 4 suppresses the spontaneous growth of chronic myelomonocytic leukemia cells. We studied the effects of IL-4 on the spontaneous proliferation of chronic myelomonocytic leukemia (CMMoL) cells in vitro. IL-4 (100 U/ml) suppressed the spontaneous DNA synthesis by approximately 50% in 5 of 8 cases examined. IL-4 (100 U/ml) also inhibited the spontaneous colony formation by CMMoL cells in a methylcellulose culture by 50-97% in all of the 10 cases in which spontaneous colonies were formed. This IL-4-mediated suppression of the growth of CMMoL cells was completely abolished by the addition of anti-IL-4 neutralizing antibodies. The spontaneous CMMoL colonies were substantially suppressed by the addition of either anti-IL-6 or anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) antibodies to the colony assay system: the addition of both anti-IL-6 and anti-GM-CSF antibodies resulted in greater than 80% inhibition of the colony formation by CMMoL cells. On the other hand, none of anti-IL-1-beta, anti-granulocyte-CSF, anti-macrophage-CSF, or anti-tumor necrosis factor-alpha antibodies affected the CMMoL colony formation. In the supernatants from 24-h cultures of CMMoL cells, high levels of IL-6 and GM-CSF were demonstrated in 9 of 9 and 2 of 9 cases examined, respectively. IL-4 (100 U/ml) almost completely inhibited the secretion of IL-6 and GM-CSF by CMMoL cells. These observations suggest that IL-4 suppresses the spontaneous proliferation of CMMoL cells by inhibiting their production of IL-6 and/or GM-CSF, both of which could act in vitro as an autocrine growth factor for CMMoL cells.
A cell cycle-responsive transcriptional control element and a negative control element in the gene encoding DNA polymerase alpha in Saccharomyces cerevisiae. Transcription of the POL1 gene of Saccharomyces cerevisiae, which encodes DNA polymerase alpha, the DNA polymerase required for the initiation of DNA replication, has previously been shown to be cell cycle regulated. To understand how the POL1 gene senses cell cycle position, we have investigated the cis-acting elements that respond to the factors that govern cell cycle progression. In this report we demonstrate that a region of 54 nucleotides containing the repeated element ACGCGT, which conforms to an Mlu I restriction endonuclease recognition site, contains all information necessary for transcriptional activation and cell cycle responsiveness. Although oligonucleotides lacking either one or both of the repeated Mlu I sites can function as an upstream activating sequence, the presence of at least one Mlu I site stimulates expression and, moreover, is absolutely essential for cell cycle regulation. A synthetic oligonucleotide corresponding to a 19-base-pair sequence in the POL1 promoter containing one Mlu I site can function as an autonomous cell cycle-responsive upstream element (upstream activation sequence) with temporal regulation indistinguishable from that previously described for the POL1 gene. Thus, the Mlu I site is an essential part of a cis-acting element responsible for the observed periodic activation. This sequence differs from previously defined cell cycle-responsive transcriptional control elements in the yeast HO endonuclease and histone genes. We also present evidence for a negative regulatory element in the 5' flanking region of the Mlu I upstream activation sequence.
Resolution of chronic pelvic pain after laparoscopic lysis of adhesions. Thirty women undergoing laparoscopic lysis of adhesions for the treatment of chronic pelvic pain were prospectively evaluated for the presence of a chronic pain syndrome. At follow-up, of those with chronic pain syndrome (10), four (40%) reported continued improvement or resolution of pain during daily activities of dyspareunia, whereas of those without chronic pain syndrome (20), 15 (75%) were better (p = 0.06). When these two complaints are evaluated individually, both pain during daily activities (p less than 0.05) and dyspareunia (p less than 0.05) are more likely to improve after lysis of adhesions in women without chronic pain syndrome. Prognosis was not related to the number of previous operations, adhesion score, or other physical parameters. Laparoscopic lysis of adhesions is generally worthwhile in the treatment of chronic pelvic pain, although the presence of psychosocial compromise warrants preoperative evaluation and concomitant treatment.
Colectomy, mucosal proctectomy, and ileal pouch-anal anastomosis. A prospective trial of optimal antibiotic management. The ideal prophylactic antibiotic regimen has not been established for patients undergoing colectomy, mucosal proctectomy, and endorectal ileoanal anastomosis, a prolonged operation frequently accompanied by abdominal and pelvic contamination and associated with an infection rate up to 20%. The aim of this study was to evaluate, in a prospective, randomized, double-blind fashion, the efficacy of a short perioperative course compared to an extended postoperative course of intravenous antibiotics (cefoxitin) in patients undergoing colectomy with ileoanal anastomosis. Forty patients with ulcerative colitis or familial polyposis coli received a mechanical and oral antibiotic bowel preparation and a standard three-dose perioperative course of intravenous cefoxitin. Patients then were randomized to receive intravenous cefoxitin, 1 g every 6 hours, or placebo for 5 days. No differences in overall postoperative morbidity were observed and neither group developed intra-abdominal, pelvic, or wound infections. It is concluded that a standard three-dose perioperative course of intravenous antibiotics provides adequate prophylaxis in the prevention of infectious complications in patients undergoing colectomy, mucosal proctectomy, and ileoanal anastomosis.
Patient activity, sports participation, and impact loading on the durability of cemented total hip replacements. Patients with either cemented surface replacements or cemented stemmed hip prostheses and who regularly participate in sporting activities or heavy labor after total joint arthroplasty are at twice the long-term risk of requiring revision surgery for loosening as patients who are less active. For patients with surface replacement total hip arthroplasty (THA), the adverse effects of activity are greatest in patients with preoperative diagnoses other than osteoarthritis, and were seen by the sixth year postsurgery. For patients with conventional stemmed prostheses, the effects of patient activity are not seen until about ten years postsurgery. For resurfacing THA for osteoarthritis, the long-term of loosening is primarily in patients who participate in high impact activities.